p53 Expression
Published by Anonymous on 2007/9/28 (2410 reads)
1: J Dermatol. 2007 Jun;34(6):367-74.
Expression of p53 in lesions and unaffected skin of patients with plaque-type and guttate psoriasis: a quantitative comparative study.
Yazici AC, Karabulut AA, Ozen O, Ekşioğlu M, Ustün H.
Department of Dermatology, Faculty of Medicine, Mersin University, Mersin, Turkey. aycacordan@yahoo.com
Psoriasis is a common inflammatory and hyperproliferative skin disease characterized by hyperproliferation of keratinocytes. The pathogenesis of psoriasis has yet to be determined. The control of cell growth is a delicately balanced process, regulated by external signals or the internal genetic program of an individual cell. In psoriasis, these processes are disturbed and some candidate genes like p53 are suspected of being involved in the pathogenesis of the disease. The p53 protein is essential for the regulation of cell proliferation. The study was performed on 32 patients with psoriasis (24 plaque type, eight guttate type). Biopsy specimens for immunohistochemical determination of p53 protein expression were collected from both the lesional and the nonlesional skin sites that were not exposed to sun in all of the patients (n = 32). Taking the ultraviolet (UV) exposure of the skin into consideration, a third skin sample was taken from each patient (n = 7) who had lesions on the sun-exposed areas. Immunohistochemical assessment of p53 expression in skin was determined as p53 protein expression per 1000 cells (keratinocytes). The statistical analysis revealed that the expressions of p53 per 1000 cells were higher in non-sun-exposed lesional skin than the non-sun-exposed nonlesional skin, also in plaque-type psoriasis than guttate-type psoriasis (P = 0.000, P = 0.046, P = 0.037, respectively). There was a positive correlation between the p53 expression in non-sun-exposed lesional skin versus expression in sun-exposed lesional skin (cubic centimeters = 0.811, P = 0.027). Our results show a stronger association of elevated p53 expression with chronic rather than acute inflammatory psoriasis. This may indicate a mechanistic difference between plaque-type and guttate psoriasis. Alternatively, this could reflect a chronological course as the disease transitions from an acute to a chronic phase.
Publication Types:
Comparative Study
Review
PMID: 17535401 [PubMed - indexed for MEDLINE]
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2: J Investig Dermatol Symp Proc. 2005 Nov;10(2):142-52.
Melanocyte and keratinocyte carcinogenesis: p53 family protein activities and intersecting mRNA expression profiles.
Kulesz-Martin M, Lagowski J, Fei S, Pelz C, Sears R, Powell MB, Halaban R, Johnson J.
Department of Dermatology, Oregon Health & Science University, Portland, Oregon 97239, USA. kuleszma@ohsu.edu
Melanocytes and keratinocytes were analyzed for potential roles of p53, p73, and p63 tumor suppressor family proteins and of malignancy-specific gene expression changes in the etiology of multi-step cancer. Melanocytes expressed deltaNp73alpha, two p63 isoforms and p53. Although p21 and Noxa mRNA levels increased following DNA damage, p53 family member binding to p21 and Noxa DNA probes was undetectable, suggesting p53 family-independent responses. In contrast, keratinocytes expressed multiple isoforms each of p73 and p63 that were induced to bind p21 and Noxa DNA probes after ionizing (IR) or after ultraviolet B (UVB) irradiation, correlating with p21 and Noxa mRNA induction and with apoptosis. Interestingly, IR-resistant malignant melanocytes and keratinocytes both exhibited Noxa mRNA induction after UVB treatment, correlating with DNA binding of p53 family proteins to the Noxa probe only in keratinocytes. To uncover other malignancy-specific events, we queried mouse initiated keratinocyte clones for early changes that were exacerbated in malignant derivatives and also differentially expressed in human advanced melanoma versus normal melanocytes. Using a new method for ranking and normalization of microarray data for 5000 probe sets, 27 upregulated and 13 downregulated genes satisfied our query. Of these, the majority was associated with late-stage human cancers and six were novel genes. Thus, clonal lineage mouse models representing early through late cancer progression stages may inform the focus on early, potentially causal events from microarray studies of human cancers, facilitating prognosis and molecular therapy.
Publication Types:
Research Support, N.I.H., Extramural
Review
PMID: 16363065 [PubMed - indexed for MEDLINE]
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3: Cornea. 2005 Jul;24(5):583-6.
p53 Expression in pterygium by immunohistochemical analysis: a series report of 127 cases and review of the literature.
Tsai YY, Chang KC, Lin CL, Lee H, Tsai FJ, Cheng YW, Tseng SH.
Department of Ophthalmology, China Medical University Hospital, Taichung, Taiwan.
PURPOSE: To assess the p53 protein expression in pterygial tissue and to review all immunohistochemical studies on pterygium from Medline to evaluate the roles of age, gender, race, p53 antibody, cutoff levels of immunohistochemical analysis, parts of pterygium, p53 gene mutation spectrum, and primary or recurrent pterygium on the p53 staining results. METHODS: Immunohistochemical staining was performed on 127 pterygial specimens and 18 normal conjunctival samples. All 8 immunohistochemical studies on p53 expression in pterygium from Medline were reviewed. RESULTS: Among the 127 pterygial samples, there were 29 specimens (22.8%) positive for p53 expression. There was no significant difference between the p53-positive and p53-negative groups with respect to age or gender. CONCLUSION: The positive rate of p53 staining in 8 immunohistochemical studies was 7.9%, 36.8%, 37.5%, 38.1%, 50%, 53.8%, 60%, and 100%, respectively. p53 protein antibody, cutoff level, race, and p53 gene mutational spectra all affect the results on the p53 staining. Different parts of pterygium and gender merit further evaluation in their role on p53 staining result.
Publication Types:
Review
PMID: 15968165 [PubMed - indexed for MEDLINE]
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4: Arch Dermatol Res. 2005 May;296(11):509-13. Epub 2005 Apr 1.
Increased expression of p53 and p21 (Waf1/Cip1) in the lesional skin of bleomycin-induced scleroderma.
Yamamoto T, Nishioka K.
Department of Dermatology, Tokyo Medical and Dental University, School of Medicine, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8519, Japan. yamamoto.derm@med.tmd.ac.jp
Systemic sclerosis (SSc) is a connective tissue disorder characterized by excessive deposition of extracellular matrix in the affected skin as well as various internal organs, vascular injury and immune abnormality; however, the etiology of SSc remains still unknown. We previously established an experimental mouse model for scleroderma by repeated local injections of bleomycin, a DNA damaging agent. In this study, we examined the induction of apoptosis and the expression of p53, p21 (Waf1/Cip1), and proliferating cell nuclear antigen (PCNA) in the lesional skin following bleomycin exposure in this model. Dermal sclerosis was induced by alternate day's injections of bleomycin for 4 weeks. TUNEL assay showed that apoptotic cells began to appear at 1 week after bleomycin exposure, and were prominently detected at 3-4 weeks. Immunohistochemical examination showed increased expression of p53 and p21 mainly in the infiltrating mononuclear cells at 2 weeks after bleomycin treatment. Bleomycin treatment markedly enhanced PCNA expression at 1-2 weeks, mainly in mesenchyme, as compared with control phosphate buffered saline treatment. Reverse transcriptase-polymerase chain reaction analysis showed that the expression of p53 and p21 mRNA was concurrently upregulated at 1-2 weeks after bleomycin treatment. Taken together, coordinate increased levels of p53 and p21 preceded the maximal induction of apoptosis and dermal sclerosis. Our findings suggest that apoptotic processes are involved in the pathophysiology of bleomycin-induced scleroderma, which may be mediated, in part, by the upregulation of p53 and p21.
Publication Types:
Review
PMID: 15803328 [PubMed - indexed for MEDLINE]
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5: Pathol Oncol Res. 2005;11(1):45-9. Epub 2005 Mar 31.
Expression of p53, Ki-67 and Bcl-2 in parathyroid adenoma and residual normal tissue.
Hadar T, Shvero J, Yaniv E, Ram E, Shvili I, Koren R.
Department of Otolaryngology--Head and Neck Surgery, Rabin Medical Center, Petah Tikva and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
The aim of this study was to investigate the expression of Ki-67, bcl-2 and p53 in parathyroid adenomas and their residual rim of normal parathyroid tissue. Specimens from 26 parathyroid adenomas were studied by immunohistochemical analysis for Ki-67, bcl-2 and p53 expression. Positive findings were noted for p53 in 4 (15%) adenomas and none of the residual rims of normal parathyroid tissue (p = 0.055); for Ki-67 in 15 (56%) adenomas and none of the residual rims of normal parathyroid tissue (p = 0.00002); and for bcl-2 in 19 (73%) adenomas and 8 (31%) residual rims of normal parathyroid tissue (p < 0.01). The high rate of Ki-67 expression may indicate susceptibility of parathyroid adenomas to clonal proliferation. The weak immunoreactive expression of p53, combined with a relatively strong expression of bcl-2, may contribute to the characteristic slow progression of these tumors.
Publication Types:
Review
PMID: 15800682 [PubMed - indexed for MEDLINE]
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6: Clin Otolaryngol Allied Sci. 2004 Dec;29(6):698-704.
Molecular markers in dysplasia of the larynx: expression of cyclin-dependent kinase inhibitors p21, p27 and p53 tumour suppressor gene in predicting cancer risk.
Jeannon JP, Soames JV, Aston V, Stafford FW, Wilson JA.
Department of Otolaryngology Head and Neck Surgery, University of Newcastle-upon-Tyne, Tyne and Wear, UK. jpjeannon@doctors.org.uk
Premalignant conditions affect the larynx. Dysplasia can progress in severity resulting in cancer depending on many clinical, pathological and molecular factors. The purpose of this study was to examine the expression of the p21 and p27 cyclin-dependent kinase inhibitors and p53 tumour suppressor gene in dysplasia of the larynx. A total of 114 cases of untreated dysplasia were selected from the archives of the University of Newcastle. p21, p27 and p53 immunohistochemistry was performed and the cases followed up. Twenty-eight dysplasias (24%) subsequently developed into cancers. Expression of the molecular factors studied was not associated with cancer progression. p53 expression was associated with smoking (P = 0.005). In contrast, grade of dysplasia was significantly associated with cancer risk (odds ratio 6.7; P = 0.0001). The majority (75%) of cancers were detected within 12 months of dysplasia being diagnosed.
Publication Types:
Research Support, Non-U.S. Gov't
Review
PMID: 15533163 [PubMed - indexed for MEDLINE]
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7: Ann N Y Acad Sci. 2004 Jun;1019:330-2.
The proinflammatory phenotype of senescent cells: the p53-mediated ICAM-1 expression.
Kletsas D, Pratsinis H, Mariatos G, Zacharatos P, Gorgoulis VG.
Laboratory of Cell Proliferation and Ageing, Institute of Biology, National Centre of Scientific Research Demokritos, Athens, Greece. dkletsas@bio.demokritos.gr
Senescent cells are characterized by the activation of the tumor suppressor protein p53 and consequently their inability to proliferate. However, their phenotype is not restricted to the exhaustion of their replicative potential, as they also exhibit a proinflammatory phenotype, which could possibly contribute to the aging process. Intercellular adhesion molecule-1 (ICAM-1) is one of the molecules involved in inflammatory response that is overexpressed in senescent cells and aged tissues. Although the role of the nuclear factor-kappa B (NF-kappa B) signaling cascade is crucial in ICAM-1 activation, we have shown that p53 directly activates the expression of ICAM-1 in an NF-kappa B-independent manner. This may link p53 to ICAM-1 function and consequently to the aging process and to various age-related pathologies.
Publication Types:
Research Support, Non-U.S. Gov't
Review
PMID: 15247038 [PubMed - indexed for MEDLINE]
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8: Pneumonol Alergol Pol. 2003;71(7-8):365-70.
[p53 and HER-2/neu expression in relation to chemotherapy in non-small cell lung cancer patients]
[Article in Polish]
Fijołek J.
III Kliniki Chorób Płuc, Instytutu Gruźlicy i Chorób Płuc w Warszawie.
Publication Types:
Review
PMID: 15052971 [PubMed - indexed for MEDLINE]
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9: Nippon Rinsho. 2003 Sep;61 Suppl 7:233-6.
[Immunohistologic evaluation of TS, DPD, and p53 protein expression in patients with colorectal cancer having liver and pulmonary metastases]
[Article in Japanese]
Ishida H, Sadahiro S, Tajima T, Makuuchi H.
Department of Surgery, Tokai University, School of Medicine.
Publication Types:
Review
PMID: 14574888 [PubMed - indexed for MEDLINE]
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10: Cancer Lett. 2003 Jul 18;197(1-2):99-103.
When p53 needs p73 to be functional - forced p73 expression induces nuclear accumulation of endogenous p53 protein.
Goldschneider D, Blanc E, Raguenez G, Haddada H, Bénard J, Douc-Rasy S.
Centre National de la Recherche Scientifique, Unité Mixte de Recherche 8126, Institut Gustave Roussy, 94805 Villejuif Cedex, France.
In human neuroblastoma (NB), wild type p53 protein does not elicit its archetypal human tumor suppressive activity so far described. To elucidate this alteration, substantial investigations using NB cell lines have underscored p53 protein nuclear localization defect and/or inappropriate conformation, but no definitive evidence has been provided so far. p73, the first homologue of the p53 gene, locates at the 1p36.3 locus, which is known to be deleted in various human tumors including NB. Unlike p53 mRNA, which specifies a single protein, p73alpha mRNAs encode two types of isoform (TAp73alpha and DeltaNp73alpha) resulting from the use of two different promoters, and eliciting or lacking NH(2)-terminal transactivation domain, respectively. DeltaNp73alpha inhibits p53 pro-apoptotic function in murine developing neurons and is abundantly expressed in human undifferentiated NB tumors. However, critical issues have been raised regarding p73alpha isoform roles, and their possible link to p53 are yet to be clarified in human NB using adenoviral infection approach.
Publication Types:
Research Support, Non-U.S. Gov't
Review
PMID: 12880967 [PubMed - indexed for MEDLINE]
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11: Cancer. 2003 Jan 15;97(2):389-404.
A review of p53 expression and mutation in human benign, low malignant potential, and invasive epithelial ovarian tumors.
Kmet LM, Cook LS, Magliocco AM.
Department of Community Health Sciences, University of Calgary, Calgary, Alberta, Canada.
BACKGROUND: In the current study, the authors present pooled data from studies that investigated p53 protein expression and/or mutation in human epithelial ovarian tumors. METHODS: The English literature in the MEDLINE, PubMed, and Ingenta databases was searched to the end of the year 2000 to identify relevant studies. Data were pooled across eligible studies, and the prevalence of p53 expression and mutation among benign, low malignant potential (LMP), and invasive tumors was determined. Prevalence estimates by tumor histology, International Federation of Gynecology and Obstetrics (FIGO) stage, and grade also were calculated. RESULTS: The pooled prevalence estimate for p53 overexpression among epithelial ovarian carcinomas was 51% (95% confidence intervals [95% CI], 50-53%) compared with 17% (95% CI, 15-20%) among LMP tumors and 7% (95% CI, 5-10%) among benign tumors. p53 mutation prevalence estimates were 45% (95% CI, 42-47%), 5% (95% CI, 2-9%), and 1% (95% CI, 0-5%), respectively, for invasive, LMP, and benign tumors. The prevalence of these p53 abnormalities was found to be associated positively with increasing tumor grade and stage. Differences based on histologic subtype also were found. CONCLUSIONS: Although these pooled estimates might appear to offer support for various hypotheses regarding the role of p53 in ovarian carcinoma, the limitations inherent in these data hamper the interpretation of the significance of any of the findings. Future studies will require innovative methods to address the limitations of many previous investigations and more comprehensive investigation into defective tumor suppression mechanisms. Copyright 2003 American Cancer Society
Publication Types:
Meta-Analysis
Review
PMID: 12518363 [PubMed - indexed for MEDLINE]
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12: Cell Mol Life Sci. 2002 Aug;59(8):1274-9.
Differential display analysis of gene expression in mammals: a p53 story.
Stein S, Liang P.
Vanderbilt-Ingram Cancer Center, Department of Cancer Biology, School of Medicine, Vanderbilt University, Nashville, Tennessee 37232, USA.
Differential display is used worldwide as a method to identify changes in gene expression and to discover novel genes that are involved in important biological pathways. The principle of differential display is the systematic amplification of the 3' termini of messenger RNAs by using anchored oligo-dT primers in combination with upstream arbitrary primers. The separation of the polymerase chain reaction products by gel electrophoresis and their direct comparison allows the identification of differentially regulated genes. Recently, fluorescent differential display was established as the first nonradioactive differential display system with equivalent sensitivity to originally 33P isotopic labeling method. Because of its simplicity, sensitivity, reproducibility and automation, which increase the throughput and accuracy, differential display has become one of the most widely used gene-screening methods in biomedical research involving mammals. This chapter provides a glimpse of the application of differential display in search of target genes of the p53 tumor suppressor gene.
Publication Types:
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.
Review
PMID: 12363031 [PubMed - indexed for MEDLINE]
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13: Med Hypotheses. 2002 Feb;58(2):136-40.
P53 possibly upregulates the expression of CD58 (LFA-3) and CD59 (MIRL).
Sampaziotis F, Kokotas S, Gorgoulis VG.
Department of Histology and Embryology, Medical School, University of Athens, Greece.
P53 is an oncosuppressor protein which acts via transcriptional and non-transcriptional mechanisms. The transcriptional function of p53 is mediated by specific responsive elements (RE). In the present study we found one perfect p53 RE located in the first intron of the gene encoding for CD58 (lymphocyte function Antigen-3/LFA-3) membrane protein. Additionally, we detected one perfect p53 RE within the promoter region and one imperfect p53 RE placed in the first intron of the gene encoding for CD59 (membrane inhibitor of reactive lysis/MIRL). The results of our investigation suggest that p53 may enhance the transcription of both CD59 and CD58 and imply a novel role for p53 as a direct regulator of the immune response. Copyright 2002 Harcourt Publishers Ltd.
Publication Types:
Review
PMID: 11812190 [PubMed - indexed for MEDLINE]
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14: Int J Cancer. 2002 Feb 1;97(4):403-9.
Molecular staging of colorectal cancer in African-American and Caucasian patients using phenotypic expression of p53, Bcl-2, MUC-1 AND p27(kip-1).
Grizzle WE, Manne U, Weiss HL, Jhala N, Talley L.
Department of Pathology, UAB Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, AL 35233-0007, USA. grizzle@path.uab.edu
The gold standard for clinical outcome of most cancers has been the clinical and pathologic staging of the tumors after surgery. For colorectal cancer (CRC), nodal involvement at the time the primary tumor is resected has been the most reliable indicator of clinical outcome; however, recently, combinations of molecular markers have been reported to be equivalent to pathologic or clinical staging in predicting clinical outcome. In addition, molecular markers can be used in conjunction with clinical or pathologic staging to provide a stronger indicator of clinical outcome than staging alone. We propose that "molecular staging" be added to pathologic staging to aid in predicting clinical outcome and making therapeutic decisions for colorectal cancers, especially stage II and III CRCs. We have reported that the clinical usefulness of most molecular markers varies with the ethnic group of the patients and the anatomic location of CRCs; this complicates the evaluation of prognostic biomarkers and requires much larger numbers of cases to be evaluated. Nevertheless, nuclear accumulation of p53 (p53(nac)) and phenotypic expression of Bcl-2, MUC-1 and p27(kip-1) may be molecular markers approaching acceptance for use in molecular staging of specific subgroups of colorectal cancers. Copyright 2001 Wiley-Liss, Inc.
Publication Types:
Comparative Study
Research Support, U.S. Gov't, P.H.S.
Review
PMID: 11802199 [PubMed - indexed for MEDLINE]
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15: Lung Cancer. 2002 Jan;35(1):35-41.
Prognostic relevance of proliferating cell nuclear antigen and p53 expression in non-small cell lung cancer.
Dworakowska D, Gózdz S, Jassem E, Badzio A, Kobierska G, Urbaniak A, Skokowski J, Damps I, Jassem J.
Department of Oncology and Radiotherapy, Medical University of Gdansk, 7 Debinki St. 80-211, Gdansk, Poland.
Prognostic value of p53 and PCNA expression in non-small cell lung cancer (NSCLC) remains controversial. In this study we determined the relevance of these abnormalities in terms of overall survival and disease-free survival in 95 NSCLC patients who underwent curative pulmonary resection. Expression of p53 was found in 44 samples (45%), expression of PCNA-in 79 samples (83%), and expression of both markers-in 35 samples (36%). There was no relationship between expression of either protein and major clinicopathological characteristics. Median survival for patients with and without p53 expression was 36 and 33 months, respectively and 5-year survival probability-29 and 37%, respectively (P=0.73). Median survival for patients with and without PCNA expression was 36 and 27 months, respectively and 5-year survival probability-35 and 25%, respectively (P=0.60). There was no significant difference in overall survival between particular groups of patients with tumors carrying four possible p53/PCNA phenotypes. In multivariate analysis including patient age, sex, tumor stage, tumor type and differentiation, p53 and PCNA expression, the only variable important for survival was stage of disease. These results suggest the lack of prognostic relevance of p53 and PCNA expression in surgically treated NSCLC patients.
Publication Types:
Comparative Study
Review
PMID: 11750711 [PubMed - indexed for MEDLINE]
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16: Eur Arch Otorhinolaryngol. 2001 Sep;258(7):329-35.
Over-expression of p53 and c-erbB-2 oncoproteins in laryngeal carcinoma.
Kazkayasi M, Hücümenoğlu S, Siriner GI, Hücümenoğlu M.
mkazkaya@ttnet.net.tr
An immunohistochemical analysis of over-expression of p53 and c-erbB-2 proteins was performed on 27 biopsies of laryngeal carcinoma. The aim of this study was to investigate whether there is a correlation between over-expression of these proteins and the clinicopathological features of the tumor and to reveal any possible prognostic value. Paraffin sections of laryngeal carcinoma were studied using immunohistochemical staining with mouse and rabbit monoclonal antibodies, respectively, for p53 and c-erbB-2 proteins. The positive controls were paraffin-embedded specimens from ten breast carcinomas previously shown to express these proteins. Ten benign laryngeal nodules were immunohistochemically stained as negative controls. Samples from 74% of 27 patients with laryngeal carcinomas demonstrated positive nuclear and cytoplasmic (or membranous) staining for p53 protein and 48% were positive for c-erbB-2 protein. In the present study, while there was a slight difference in the frequency of p53 over-expression among stage I-II and stage III-IV tumors, there was no difference in the frequency of p53 over-expression among primary and recurrent tumors. There was no statistically significant correlation between over-expression of the p53 and c-erbB-2 proteins and the age of the patients, tumor site, tumor grade, clinical stage, histopathological grading of the tumor, alcohol consumption, and clinical outcome. There was a statistically significant correlation between immunostaining of p53 and c-erbB-2 proteins (P = 0.037). While it was found that over-expression of p53 was significantly associated with the presence of lymph node metastasis (P = 0.006), there was no association between the expression of c-erbB-2 and lymph node status. The data demonstrated increased expression of p53 and c-erbB-2 proteins, presumed to be mutant, in laryngeal carcinomas. Hence, we conclude that p53 and c-erbB-2 over-expression as detected by immunohistochemical staining in larynx carcinomas is not predictive of poor survival or disease-free survival.
Publication Types:
Review
PMID: 11699821 [PubMed - indexed for MEDLINE]
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17: Methods Mol Biol. 2001;175:495-520.
Gene therapy approaches to sensitization of human prostate carcinoma to cisplatin by adenoviral expression of p53 and by antisense jun kinase oligonucleotide methods.
Gjerset R, Haghighi A, Lebedeva S, Mercola D.
Sidney Kimmel Cancer Center, San Diego, CA, USA.
Publication Types:
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Research Support, U.S. Gov't, P.H.S.
Review
PMID: 11462854 [PubMed - indexed for MEDLINE]
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18: Cell Death Differ. 1999 Dec;6(12):1154-61.
Comment in:
Cell Death Differ. 1999 Dec;6(12):1143.
p53 family genes: structural comparison, expression and mutation.
Ikawa S, Nakagawara A, Ikawa Y.
Institute of Development, Aging and Cancer, Tohoku University, Sendai 980-8575, Japan.
The p53-related genes, p51/p63 and p73, have been isolated respectively from cDNA libraries of skeletal muscle and the brain, and their structural features and biological functions have been compared. High expression of p51A (TAp63gamma) in the skeletal muscle tissue drove us to investigate a differentiation-inducible myoblastic cell line which showed increased p51A expression after differentiation induction. Tissue-specific expression was further confirmed by reverse transcriptase-polymerase chain reaction (RT - PCR) using primers specific for DeltaN (TA-domain lacking p51), p51A, and p51B expression. p51A alone induced erythrodifferentiation when expressed in the erythroleukemia line (Tg-gp55-1-2-3) expressing a temperature-sensitive mutant of p53, and induced remarkable apoptosis when wild-type p53 expression was induced by the temperature shift to 32 degrees C. Human p51A and p53 were introduced exogenously into the above erythroleukemia cells, and although their expression was rather low, both p51A and p53 proteins were induced by DNA-damaging treatment with UV and ActinomycinD. However, the protein-protein interactions analyzed by a yeast two-hybrid assay between p51 and p53, between p51 and p73, and between p51 and oncoproteins showed that p51 is functionally rather distant from p53. Extensive mutation analysis of p51/p63 in human tumors revealed only four mutations in 80 non-small cell lung carcinomas; two adenocarcinoma cases possessing Glu31His mutations in the transactivation domain (TA) domain, suggesting that p51/p63 is not a Knudson type tumor suppressor gene. Mutation and loss of heterozygosity (LOH) of p73, deregulated expression of p73 and loss of imprinting of p73 are also discussed.
Publication Types:
Review
PMID: 10637430 [PubMed - indexed for MEDLINE]
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19: Mod Pathol. 1999 Dec;12(12):1158-66.
p53 and P-glycoprotein expression do not correlate with survival in nonsmall cell lung cancer: a long-term study and literature review.
Haque AK, Adegboyega P, Al-Salameh A, Vrazel DP, Zwischenberger J.
Department of Pathology, University of Texas Medical Branch at Galveston, 77555-0743, USA. Ahaque@utmb.edu
This long-term study includes up to 13 years of follow-up on 56 patients who underwent surgical resection of nonsmall cell lung cancers (NSCLC) at the University of Texas Medical Branch. The purpose of this study was to investigate whether p53 and P-glycoprotein expression in the tumor correlates with survival. The study included 35 men and 21 women with mean age at diagnosis of 63.6 years and 58.0 years, respectively. Follow-up ranged from four to 156 months (mean, 52 mo). Actual five-year survival was 50% and 10-year survival was 22%. There were 25 patients who survived more than 60 months. Commercially available antibodies, DO-7 monoclonal antibody to p53 protein, and NCL-PGLyp polyclonal antibody to P-glycoprotein were used. p53 expression was seen in 45%, and P-glycoprotein expression was seen in 61% of the tumors, using standard immunohistochemical techniques. Expression of p53 showed correlation with Caucasian race and a better, although nonsignificant, five-year survival. P-glycoprotein expression showed a highly significant association with squamous cell carcinoma. No association was found between P-glycoprotein expression and survival. A negative association was seen between p53 and P-glycoprotein expression. Using nonparametric analysis, significant correlations were found between female sex and younger age at diagnosis of lung cancer compared with males, adenocarcinoma, and Caucasian race. Using Kaplan-Meier survival tables, significantly better five-year survival was seen with stage I tumors, negative lymph nodes at surgery, Caucasian race, and well-differentiated tumors. Stage I and negative lymph nodes at surgery showed an independent significant association with long-term (>5-yr) survival. This study indicates that p53 and P-glycoprotein may not be useful as immunohistochemical markers for guiding therapy and predicting survival in NSCLC.
Publication Types:
Review
PMID: 10619270 [PubMed - indexed for MEDLINE]
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20: Oncogene. 1999 Dec 13;18(53):7676-80.
Alternative pathways for the extension of cellular life span: inactivation of p53/pRb and expression of telomerase.
Vaziri H, Benchimol S.
Stanford University School of Medicine, Department of Molecular Pharmacology, Edward's Building, 300 Pasteur Drive Stanford, California, CA 94305-5332, USA.
Telomere shortening may be one of several factors that contribute to the onset of senescence in human cells. The p53 and pRb pathways are involved in the regulation of cell cycle progression from G1 into S phase and inactivation of these pathways leads to extension of life span. Short dysfunctional telomeres may be perceived as damaged DNA and may activate these pathways, leading to prolonged arrest in G1, typical of cells in senescence. Inactivation of the p53 and pRb pathways, however, does not lead to cell immortalization. Cells that overcome senescence and have an extended life span continue to lose telomeric DNA and subsequently enter a second phase of growth arrest termed 'crisis'. Forced expression of telomerase in human cells leads to the elongation of telomeres and immortalization. The development of human cancer is frequently associated with the inactivation of the pRb and p53 pathways, attesting to the importance of senescence in restricting the tumor-forming ability of human cells. Cancer cells must also maintain telomere length and, in the majority of cases, this is associated with expression of telomerase activity.
Publication Types:
Research Support, Non-U.S. Gov't
Review
PMID: 10618707 [PubMed - indexed for MEDLINE]
Expression of p53 in lesions and unaffected skin of patients with plaque-type and guttate psoriasis: a quantitative comparative study.
Yazici AC, Karabulut AA, Ozen O, Ekşioğlu M, Ustün H.
Department of Dermatology, Faculty of Medicine, Mersin University, Mersin, Turkey. aycacordan@yahoo.com
Psoriasis is a common inflammatory and hyperproliferative skin disease characterized by hyperproliferation of keratinocytes. The pathogenesis of psoriasis has yet to be determined. The control of cell growth is a delicately balanced process, regulated by external signals or the internal genetic program of an individual cell. In psoriasis, these processes are disturbed and some candidate genes like p53 are suspected of being involved in the pathogenesis of the disease. The p53 protein is essential for the regulation of cell proliferation. The study was performed on 32 patients with psoriasis (24 plaque type, eight guttate type). Biopsy specimens for immunohistochemical determination of p53 protein expression were collected from both the lesional and the nonlesional skin sites that were not exposed to sun in all of the patients (n = 32). Taking the ultraviolet (UV) exposure of the skin into consideration, a third skin sample was taken from each patient (n = 7) who had lesions on the sun-exposed areas. Immunohistochemical assessment of p53 expression in skin was determined as p53 protein expression per 1000 cells (keratinocytes). The statistical analysis revealed that the expressions of p53 per 1000 cells were higher in non-sun-exposed lesional skin than the non-sun-exposed nonlesional skin, also in plaque-type psoriasis than guttate-type psoriasis (P = 0.000, P = 0.046, P = 0.037, respectively). There was a positive correlation between the p53 expression in non-sun-exposed lesional skin versus expression in sun-exposed lesional skin (cubic centimeters = 0.811, P = 0.027). Our results show a stronger association of elevated p53 expression with chronic rather than acute inflammatory psoriasis. This may indicate a mechanistic difference between plaque-type and guttate psoriasis. Alternatively, this could reflect a chronological course as the disease transitions from an acute to a chronic phase.
Publication Types:
Comparative Study
Review
PMID: 17535401 [PubMed - indexed for MEDLINE]
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2: J Investig Dermatol Symp Proc. 2005 Nov;10(2):142-52.
Melanocyte and keratinocyte carcinogenesis: p53 family protein activities and intersecting mRNA expression profiles.
Kulesz-Martin M, Lagowski J, Fei S, Pelz C, Sears R, Powell MB, Halaban R, Johnson J.
Department of Dermatology, Oregon Health & Science University, Portland, Oregon 97239, USA. kuleszma@ohsu.edu
Melanocytes and keratinocytes were analyzed for potential roles of p53, p73, and p63 tumor suppressor family proteins and of malignancy-specific gene expression changes in the etiology of multi-step cancer. Melanocytes expressed deltaNp73alpha, two p63 isoforms and p53. Although p21 and Noxa mRNA levels increased following DNA damage, p53 family member binding to p21 and Noxa DNA probes was undetectable, suggesting p53 family-independent responses. In contrast, keratinocytes expressed multiple isoforms each of p73 and p63 that were induced to bind p21 and Noxa DNA probes after ionizing (IR) or after ultraviolet B (UVB) irradiation, correlating with p21 and Noxa mRNA induction and with apoptosis. Interestingly, IR-resistant malignant melanocytes and keratinocytes both exhibited Noxa mRNA induction after UVB treatment, correlating with DNA binding of p53 family proteins to the Noxa probe only in keratinocytes. To uncover other malignancy-specific events, we queried mouse initiated keratinocyte clones for early changes that were exacerbated in malignant derivatives and also differentially expressed in human advanced melanoma versus normal melanocytes. Using a new method for ranking and normalization of microarray data for 5000 probe sets, 27 upregulated and 13 downregulated genes satisfied our query. Of these, the majority was associated with late-stage human cancers and six were novel genes. Thus, clonal lineage mouse models representing early through late cancer progression stages may inform the focus on early, potentially causal events from microarray studies of human cancers, facilitating prognosis and molecular therapy.
Publication Types:
Research Support, N.I.H., Extramural
Review
PMID: 16363065 [PubMed - indexed for MEDLINE]
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3: Cornea. 2005 Jul;24(5):583-6.
p53 Expression in pterygium by immunohistochemical analysis: a series report of 127 cases and review of the literature.
Tsai YY, Chang KC, Lin CL, Lee H, Tsai FJ, Cheng YW, Tseng SH.
Department of Ophthalmology, China Medical University Hospital, Taichung, Taiwan.
PURPOSE: To assess the p53 protein expression in pterygial tissue and to review all immunohistochemical studies on pterygium from Medline to evaluate the roles of age, gender, race, p53 antibody, cutoff levels of immunohistochemical analysis, parts of pterygium, p53 gene mutation spectrum, and primary or recurrent pterygium on the p53 staining results. METHODS: Immunohistochemical staining was performed on 127 pterygial specimens and 18 normal conjunctival samples. All 8 immunohistochemical studies on p53 expression in pterygium from Medline were reviewed. RESULTS: Among the 127 pterygial samples, there were 29 specimens (22.8%) positive for p53 expression. There was no significant difference between the p53-positive and p53-negative groups with respect to age or gender. CONCLUSION: The positive rate of p53 staining in 8 immunohistochemical studies was 7.9%, 36.8%, 37.5%, 38.1%, 50%, 53.8%, 60%, and 100%, respectively. p53 protein antibody, cutoff level, race, and p53 gene mutational spectra all affect the results on the p53 staining. Different parts of pterygium and gender merit further evaluation in their role on p53 staining result.
Publication Types:
Review
PMID: 15968165 [PubMed - indexed for MEDLINE]
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4: Arch Dermatol Res. 2005 May;296(11):509-13. Epub 2005 Apr 1.
Increased expression of p53 and p21 (Waf1/Cip1) in the lesional skin of bleomycin-induced scleroderma.
Yamamoto T, Nishioka K.
Department of Dermatology, Tokyo Medical and Dental University, School of Medicine, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8519, Japan. yamamoto.derm@med.tmd.ac.jp
Systemic sclerosis (SSc) is a connective tissue disorder characterized by excessive deposition of extracellular matrix in the affected skin as well as various internal organs, vascular injury and immune abnormality; however, the etiology of SSc remains still unknown. We previously established an experimental mouse model for scleroderma by repeated local injections of bleomycin, a DNA damaging agent. In this study, we examined the induction of apoptosis and the expression of p53, p21 (Waf1/Cip1), and proliferating cell nuclear antigen (PCNA) in the lesional skin following bleomycin exposure in this model. Dermal sclerosis was induced by alternate day's injections of bleomycin for 4 weeks. TUNEL assay showed that apoptotic cells began to appear at 1 week after bleomycin exposure, and were prominently detected at 3-4 weeks. Immunohistochemical examination showed increased expression of p53 and p21 mainly in the infiltrating mononuclear cells at 2 weeks after bleomycin treatment. Bleomycin treatment markedly enhanced PCNA expression at 1-2 weeks, mainly in mesenchyme, as compared with control phosphate buffered saline treatment. Reverse transcriptase-polymerase chain reaction analysis showed that the expression of p53 and p21 mRNA was concurrently upregulated at 1-2 weeks after bleomycin treatment. Taken together, coordinate increased levels of p53 and p21 preceded the maximal induction of apoptosis and dermal sclerosis. Our findings suggest that apoptotic processes are involved in the pathophysiology of bleomycin-induced scleroderma, which may be mediated, in part, by the upregulation of p53 and p21.
Publication Types:
Review
PMID: 15803328 [PubMed - indexed for MEDLINE]
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5: Pathol Oncol Res. 2005;11(1):45-9. Epub 2005 Mar 31.
Expression of p53, Ki-67 and Bcl-2 in parathyroid adenoma and residual normal tissue.
Hadar T, Shvero J, Yaniv E, Ram E, Shvili I, Koren R.
Department of Otolaryngology--Head and Neck Surgery, Rabin Medical Center, Petah Tikva and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
The aim of this study was to investigate the expression of Ki-67, bcl-2 and p53 in parathyroid adenomas and their residual rim of normal parathyroid tissue. Specimens from 26 parathyroid adenomas were studied by immunohistochemical analysis for Ki-67, bcl-2 and p53 expression. Positive findings were noted for p53 in 4 (15%) adenomas and none of the residual rims of normal parathyroid tissue (p = 0.055); for Ki-67 in 15 (56%) adenomas and none of the residual rims of normal parathyroid tissue (p = 0.00002); and for bcl-2 in 19 (73%) adenomas and 8 (31%) residual rims of normal parathyroid tissue (p < 0.01). The high rate of Ki-67 expression may indicate susceptibility of parathyroid adenomas to clonal proliferation. The weak immunoreactive expression of p53, combined with a relatively strong expression of bcl-2, may contribute to the characteristic slow progression of these tumors.
Publication Types:
Review
PMID: 15800682 [PubMed - indexed for MEDLINE]
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6: Clin Otolaryngol Allied Sci. 2004 Dec;29(6):698-704.
Molecular markers in dysplasia of the larynx: expression of cyclin-dependent kinase inhibitors p21, p27 and p53 tumour suppressor gene in predicting cancer risk.
Jeannon JP, Soames JV, Aston V, Stafford FW, Wilson JA.
Department of Otolaryngology Head and Neck Surgery, University of Newcastle-upon-Tyne, Tyne and Wear, UK. jpjeannon@doctors.org.uk
Premalignant conditions affect the larynx. Dysplasia can progress in severity resulting in cancer depending on many clinical, pathological and molecular factors. The purpose of this study was to examine the expression of the p21 and p27 cyclin-dependent kinase inhibitors and p53 tumour suppressor gene in dysplasia of the larynx. A total of 114 cases of untreated dysplasia were selected from the archives of the University of Newcastle. p21, p27 and p53 immunohistochemistry was performed and the cases followed up. Twenty-eight dysplasias (24%) subsequently developed into cancers. Expression of the molecular factors studied was not associated with cancer progression. p53 expression was associated with smoking (P = 0.005). In contrast, grade of dysplasia was significantly associated with cancer risk (odds ratio 6.7; P = 0.0001). The majority (75%) of cancers were detected within 12 months of dysplasia being diagnosed.
Publication Types:
Research Support, Non-U.S. Gov't
Review
PMID: 15533163 [PubMed - indexed for MEDLINE]
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7: Ann N Y Acad Sci. 2004 Jun;1019:330-2.
The proinflammatory phenotype of senescent cells: the p53-mediated ICAM-1 expression.
Kletsas D, Pratsinis H, Mariatos G, Zacharatos P, Gorgoulis VG.
Laboratory of Cell Proliferation and Ageing, Institute of Biology, National Centre of Scientific Research Demokritos, Athens, Greece. dkletsas@bio.demokritos.gr
Senescent cells are characterized by the activation of the tumor suppressor protein p53 and consequently their inability to proliferate. However, their phenotype is not restricted to the exhaustion of their replicative potential, as they also exhibit a proinflammatory phenotype, which could possibly contribute to the aging process. Intercellular adhesion molecule-1 (ICAM-1) is one of the molecules involved in inflammatory response that is overexpressed in senescent cells and aged tissues. Although the role of the nuclear factor-kappa B (NF-kappa B) signaling cascade is crucial in ICAM-1 activation, we have shown that p53 directly activates the expression of ICAM-1 in an NF-kappa B-independent manner. This may link p53 to ICAM-1 function and consequently to the aging process and to various age-related pathologies.
Publication Types:
Research Support, Non-U.S. Gov't
Review
PMID: 15247038 [PubMed - indexed for MEDLINE]
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8: Pneumonol Alergol Pol. 2003;71(7-8):365-70.
[p53 and HER-2/neu expression in relation to chemotherapy in non-small cell lung cancer patients]
[Article in Polish]
Fijołek J.
III Kliniki Chorób Płuc, Instytutu Gruźlicy i Chorób Płuc w Warszawie.
Publication Types:
Review
PMID: 15052971 [PubMed - indexed for MEDLINE]
--------------------------------------------------------------------------------
9: Nippon Rinsho. 2003 Sep;61 Suppl 7:233-6.
[Immunohistologic evaluation of TS, DPD, and p53 protein expression in patients with colorectal cancer having liver and pulmonary metastases]
[Article in Japanese]
Ishida H, Sadahiro S, Tajima T, Makuuchi H.
Department of Surgery, Tokai University, School of Medicine.
Publication Types:
Review
PMID: 14574888 [PubMed - indexed for MEDLINE]
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10: Cancer Lett. 2003 Jul 18;197(1-2):99-103.
When p53 needs p73 to be functional - forced p73 expression induces nuclear accumulation of endogenous p53 protein.
Goldschneider D, Blanc E, Raguenez G, Haddada H, Bénard J, Douc-Rasy S.
Centre National de la Recherche Scientifique, Unité Mixte de Recherche 8126, Institut Gustave Roussy, 94805 Villejuif Cedex, France.
In human neuroblastoma (NB), wild type p53 protein does not elicit its archetypal human tumor suppressive activity so far described. To elucidate this alteration, substantial investigations using NB cell lines have underscored p53 protein nuclear localization defect and/or inappropriate conformation, but no definitive evidence has been provided so far. p73, the first homologue of the p53 gene, locates at the 1p36.3 locus, which is known to be deleted in various human tumors including NB. Unlike p53 mRNA, which specifies a single protein, p73alpha mRNAs encode two types of isoform (TAp73alpha and DeltaNp73alpha) resulting from the use of two different promoters, and eliciting or lacking NH(2)-terminal transactivation domain, respectively. DeltaNp73alpha inhibits p53 pro-apoptotic function in murine developing neurons and is abundantly expressed in human undifferentiated NB tumors. However, critical issues have been raised regarding p73alpha isoform roles, and their possible link to p53 are yet to be clarified in human NB using adenoviral infection approach.
Publication Types:
Research Support, Non-U.S. Gov't
Review
PMID: 12880967 [PubMed - indexed for MEDLINE]
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11: Cancer. 2003 Jan 15;97(2):389-404.
A review of p53 expression and mutation in human benign, low malignant potential, and invasive epithelial ovarian tumors.
Kmet LM, Cook LS, Magliocco AM.
Department of Community Health Sciences, University of Calgary, Calgary, Alberta, Canada.
BACKGROUND: In the current study, the authors present pooled data from studies that investigated p53 protein expression and/or mutation in human epithelial ovarian tumors. METHODS: The English literature in the MEDLINE, PubMed, and Ingenta databases was searched to the end of the year 2000 to identify relevant studies. Data were pooled across eligible studies, and the prevalence of p53 expression and mutation among benign, low malignant potential (LMP), and invasive tumors was determined. Prevalence estimates by tumor histology, International Federation of Gynecology and Obstetrics (FIGO) stage, and grade also were calculated. RESULTS: The pooled prevalence estimate for p53 overexpression among epithelial ovarian carcinomas was 51% (95% confidence intervals [95% CI], 50-53%) compared with 17% (95% CI, 15-20%) among LMP tumors and 7% (95% CI, 5-10%) among benign tumors. p53 mutation prevalence estimates were 45% (95% CI, 42-47%), 5% (95% CI, 2-9%), and 1% (95% CI, 0-5%), respectively, for invasive, LMP, and benign tumors. The prevalence of these p53 abnormalities was found to be associated positively with increasing tumor grade and stage. Differences based on histologic subtype also were found. CONCLUSIONS: Although these pooled estimates might appear to offer support for various hypotheses regarding the role of p53 in ovarian carcinoma, the limitations inherent in these data hamper the interpretation of the significance of any of the findings. Future studies will require innovative methods to address the limitations of many previous investigations and more comprehensive investigation into defective tumor suppression mechanisms. Copyright 2003 American Cancer Society
Publication Types:
Meta-Analysis
Review
PMID: 12518363 [PubMed - indexed for MEDLINE]
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12: Cell Mol Life Sci. 2002 Aug;59(8):1274-9.
Differential display analysis of gene expression in mammals: a p53 story.
Stein S, Liang P.
Vanderbilt-Ingram Cancer Center, Department of Cancer Biology, School of Medicine, Vanderbilt University, Nashville, Tennessee 37232, USA.
Differential display is used worldwide as a method to identify changes in gene expression and to discover novel genes that are involved in important biological pathways. The principle of differential display is the systematic amplification of the 3' termini of messenger RNAs by using anchored oligo-dT primers in combination with upstream arbitrary primers. The separation of the polymerase chain reaction products by gel electrophoresis and their direct comparison allows the identification of differentially regulated genes. Recently, fluorescent differential display was established as the first nonradioactive differential display system with equivalent sensitivity to originally 33P isotopic labeling method. Because of its simplicity, sensitivity, reproducibility and automation, which increase the throughput and accuracy, differential display has become one of the most widely used gene-screening methods in biomedical research involving mammals. This chapter provides a glimpse of the application of differential display in search of target genes of the p53 tumor suppressor gene.
Publication Types:
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.
Review
PMID: 12363031 [PubMed - indexed for MEDLINE]
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13: Med Hypotheses. 2002 Feb;58(2):136-40.
P53 possibly upregulates the expression of CD58 (LFA-3) and CD59 (MIRL).
Sampaziotis F, Kokotas S, Gorgoulis VG.
Department of Histology and Embryology, Medical School, University of Athens, Greece.
P53 is an oncosuppressor protein which acts via transcriptional and non-transcriptional mechanisms. The transcriptional function of p53 is mediated by specific responsive elements (RE). In the present study we found one perfect p53 RE located in the first intron of the gene encoding for CD58 (lymphocyte function Antigen-3/LFA-3) membrane protein. Additionally, we detected one perfect p53 RE within the promoter region and one imperfect p53 RE placed in the first intron of the gene encoding for CD59 (membrane inhibitor of reactive lysis/MIRL). The results of our investigation suggest that p53 may enhance the transcription of both CD59 and CD58 and imply a novel role for p53 as a direct regulator of the immune response. Copyright 2002 Harcourt Publishers Ltd.
Publication Types:
Review
PMID: 11812190 [PubMed - indexed for MEDLINE]
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14: Int J Cancer. 2002 Feb 1;97(4):403-9.
Molecular staging of colorectal cancer in African-American and Caucasian patients using phenotypic expression of p53, Bcl-2, MUC-1 AND p27(kip-1).
Grizzle WE, Manne U, Weiss HL, Jhala N, Talley L.
Department of Pathology, UAB Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, AL 35233-0007, USA. grizzle@path.uab.edu
The gold standard for clinical outcome of most cancers has been the clinical and pathologic staging of the tumors after surgery. For colorectal cancer (CRC), nodal involvement at the time the primary tumor is resected has been the most reliable indicator of clinical outcome; however, recently, combinations of molecular markers have been reported to be equivalent to pathologic or clinical staging in predicting clinical outcome. In addition, molecular markers can be used in conjunction with clinical or pathologic staging to provide a stronger indicator of clinical outcome than staging alone. We propose that "molecular staging" be added to pathologic staging to aid in predicting clinical outcome and making therapeutic decisions for colorectal cancers, especially stage II and III CRCs. We have reported that the clinical usefulness of most molecular markers varies with the ethnic group of the patients and the anatomic location of CRCs; this complicates the evaluation of prognostic biomarkers and requires much larger numbers of cases to be evaluated. Nevertheless, nuclear accumulation of p53 (p53(nac)) and phenotypic expression of Bcl-2, MUC-1 and p27(kip-1) may be molecular markers approaching acceptance for use in molecular staging of specific subgroups of colorectal cancers. Copyright 2001 Wiley-Liss, Inc.
Publication Types:
Comparative Study
Research Support, U.S. Gov't, P.H.S.
Review
PMID: 11802199 [PubMed - indexed for MEDLINE]
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15: Lung Cancer. 2002 Jan;35(1):35-41.
Prognostic relevance of proliferating cell nuclear antigen and p53 expression in non-small cell lung cancer.
Dworakowska D, Gózdz S, Jassem E, Badzio A, Kobierska G, Urbaniak A, Skokowski J, Damps I, Jassem J.
Department of Oncology and Radiotherapy, Medical University of Gdansk, 7 Debinki St. 80-211, Gdansk, Poland.
Prognostic value of p53 and PCNA expression in non-small cell lung cancer (NSCLC) remains controversial. In this study we determined the relevance of these abnormalities in terms of overall survival and disease-free survival in 95 NSCLC patients who underwent curative pulmonary resection. Expression of p53 was found in 44 samples (45%), expression of PCNA-in 79 samples (83%), and expression of both markers-in 35 samples (36%). There was no relationship between expression of either protein and major clinicopathological characteristics. Median survival for patients with and without p53 expression was 36 and 33 months, respectively and 5-year survival probability-29 and 37%, respectively (P=0.73). Median survival for patients with and without PCNA expression was 36 and 27 months, respectively and 5-year survival probability-35 and 25%, respectively (P=0.60). There was no significant difference in overall survival between particular groups of patients with tumors carrying four possible p53/PCNA phenotypes. In multivariate analysis including patient age, sex, tumor stage, tumor type and differentiation, p53 and PCNA expression, the only variable important for survival was stage of disease. These results suggest the lack of prognostic relevance of p53 and PCNA expression in surgically treated NSCLC patients.
Publication Types:
Comparative Study
Review
PMID: 11750711 [PubMed - indexed for MEDLINE]
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16: Eur Arch Otorhinolaryngol. 2001 Sep;258(7):329-35.
Over-expression of p53 and c-erbB-2 oncoproteins in laryngeal carcinoma.
Kazkayasi M, Hücümenoğlu S, Siriner GI, Hücümenoğlu M.
mkazkaya@ttnet.net.tr
An immunohistochemical analysis of over-expression of p53 and c-erbB-2 proteins was performed on 27 biopsies of laryngeal carcinoma. The aim of this study was to investigate whether there is a correlation between over-expression of these proteins and the clinicopathological features of the tumor and to reveal any possible prognostic value. Paraffin sections of laryngeal carcinoma were studied using immunohistochemical staining with mouse and rabbit monoclonal antibodies, respectively, for p53 and c-erbB-2 proteins. The positive controls were paraffin-embedded specimens from ten breast carcinomas previously shown to express these proteins. Ten benign laryngeal nodules were immunohistochemically stained as negative controls. Samples from 74% of 27 patients with laryngeal carcinomas demonstrated positive nuclear and cytoplasmic (or membranous) staining for p53 protein and 48% were positive for c-erbB-2 protein. In the present study, while there was a slight difference in the frequency of p53 over-expression among stage I-II and stage III-IV tumors, there was no difference in the frequency of p53 over-expression among primary and recurrent tumors. There was no statistically significant correlation between over-expression of the p53 and c-erbB-2 proteins and the age of the patients, tumor site, tumor grade, clinical stage, histopathological grading of the tumor, alcohol consumption, and clinical outcome. There was a statistically significant correlation between immunostaining of p53 and c-erbB-2 proteins (P = 0.037). While it was found that over-expression of p53 was significantly associated with the presence of lymph node metastasis (P = 0.006), there was no association between the expression of c-erbB-2 and lymph node status. The data demonstrated increased expression of p53 and c-erbB-2 proteins, presumed to be mutant, in laryngeal carcinomas. Hence, we conclude that p53 and c-erbB-2 over-expression as detected by immunohistochemical staining in larynx carcinomas is not predictive of poor survival or disease-free survival.
Publication Types:
Review
PMID: 11699821 [PubMed - indexed for MEDLINE]
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17: Methods Mol Biol. 2001;175:495-520.
Gene therapy approaches to sensitization of human prostate carcinoma to cisplatin by adenoviral expression of p53 and by antisense jun kinase oligonucleotide methods.
Gjerset R, Haghighi A, Lebedeva S, Mercola D.
Sidney Kimmel Cancer Center, San Diego, CA, USA.
Publication Types:
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Research Support, U.S. Gov't, P.H.S.
Review
PMID: 11462854 [PubMed - indexed for MEDLINE]
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18: Cell Death Differ. 1999 Dec;6(12):1154-61.
Comment in:
Cell Death Differ. 1999 Dec;6(12):1143.
p53 family genes: structural comparison, expression and mutation.
Ikawa S, Nakagawara A, Ikawa Y.
Institute of Development, Aging and Cancer, Tohoku University, Sendai 980-8575, Japan.
The p53-related genes, p51/p63 and p73, have been isolated respectively from cDNA libraries of skeletal muscle and the brain, and their structural features and biological functions have been compared. High expression of p51A (TAp63gamma) in the skeletal muscle tissue drove us to investigate a differentiation-inducible myoblastic cell line which showed increased p51A expression after differentiation induction. Tissue-specific expression was further confirmed by reverse transcriptase-polymerase chain reaction (RT - PCR) using primers specific for DeltaN (TA-domain lacking p51), p51A, and p51B expression. p51A alone induced erythrodifferentiation when expressed in the erythroleukemia line (Tg-gp55-1-2-3) expressing a temperature-sensitive mutant of p53, and induced remarkable apoptosis when wild-type p53 expression was induced by the temperature shift to 32 degrees C. Human p51A and p53 were introduced exogenously into the above erythroleukemia cells, and although their expression was rather low, both p51A and p53 proteins were induced by DNA-damaging treatment with UV and ActinomycinD. However, the protein-protein interactions analyzed by a yeast two-hybrid assay between p51 and p53, between p51 and p73, and between p51 and oncoproteins showed that p51 is functionally rather distant from p53. Extensive mutation analysis of p51/p63 in human tumors revealed only four mutations in 80 non-small cell lung carcinomas; two adenocarcinoma cases possessing Glu31His mutations in the transactivation domain (TA) domain, suggesting that p51/p63 is not a Knudson type tumor suppressor gene. Mutation and loss of heterozygosity (LOH) of p73, deregulated expression of p73 and loss of imprinting of p73 are also discussed.
Publication Types:
Review
PMID: 10637430 [PubMed - indexed for MEDLINE]
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19: Mod Pathol. 1999 Dec;12(12):1158-66.
p53 and P-glycoprotein expression do not correlate with survival in nonsmall cell lung cancer: a long-term study and literature review.
Haque AK, Adegboyega P, Al-Salameh A, Vrazel DP, Zwischenberger J.
Department of Pathology, University of Texas Medical Branch at Galveston, 77555-0743, USA. Ahaque@utmb.edu
This long-term study includes up to 13 years of follow-up on 56 patients who underwent surgical resection of nonsmall cell lung cancers (NSCLC) at the University of Texas Medical Branch. The purpose of this study was to investigate whether p53 and P-glycoprotein expression in the tumor correlates with survival. The study included 35 men and 21 women with mean age at diagnosis of 63.6 years and 58.0 years, respectively. Follow-up ranged from four to 156 months (mean, 52 mo). Actual five-year survival was 50% and 10-year survival was 22%. There were 25 patients who survived more than 60 months. Commercially available antibodies, DO-7 monoclonal antibody to p53 protein, and NCL-PGLyp polyclonal antibody to P-glycoprotein were used. p53 expression was seen in 45%, and P-glycoprotein expression was seen in 61% of the tumors, using standard immunohistochemical techniques. Expression of p53 showed correlation with Caucasian race and a better, although nonsignificant, five-year survival. P-glycoprotein expression showed a highly significant association with squamous cell carcinoma. No association was found between P-glycoprotein expression and survival. A negative association was seen between p53 and P-glycoprotein expression. Using nonparametric analysis, significant correlations were found between female sex and younger age at diagnosis of lung cancer compared with males, adenocarcinoma, and Caucasian race. Using Kaplan-Meier survival tables, significantly better five-year survival was seen with stage I tumors, negative lymph nodes at surgery, Caucasian race, and well-differentiated tumors. Stage I and negative lymph nodes at surgery showed an independent significant association with long-term (>5-yr) survival. This study indicates that p53 and P-glycoprotein may not be useful as immunohistochemical markers for guiding therapy and predicting survival in NSCLC.
Publication Types:
Review
PMID: 10619270 [PubMed - indexed for MEDLINE]
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20: Oncogene. 1999 Dec 13;18(53):7676-80.
Alternative pathways for the extension of cellular life span: inactivation of p53/pRb and expression of telomerase.
Vaziri H, Benchimol S.
Stanford University School of Medicine, Department of Molecular Pharmacology, Edward's Building, 300 Pasteur Drive Stanford, California, CA 94305-5332, USA.
Telomere shortening may be one of several factors that contribute to the onset of senescence in human cells. The p53 and pRb pathways are involved in the regulation of cell cycle progression from G1 into S phase and inactivation of these pathways leads to extension of life span. Short dysfunctional telomeres may be perceived as damaged DNA and may activate these pathways, leading to prolonged arrest in G1, typical of cells in senescence. Inactivation of the p53 and pRb pathways, however, does not lead to cell immortalization. Cells that overcome senescence and have an extended life span continue to lose telomeric DNA and subsequently enter a second phase of growth arrest termed 'crisis'. Forced expression of telomerase in human cells leads to the elongation of telomeres and immortalization. The development of human cancer is frequently associated with the inactivation of the pRb and p53 pathways, attesting to the importance of senescence in restricting the tumor-forming ability of human cells. Cancer cells must also maintain telomere length and, in the majority of cases, this is associated with expression of telomerase activity.
Publication Types:
Research Support, Non-U.S. Gov't
Review
PMID: 10618707 [PubMed - indexed for MEDLINE]
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