Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P04637 (p53)
 77,613 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The human analogue of the mouse double minute-2 (MDM-2) protein binds to p53 protein and abrogates its tumor-suppressing activity. MDM-2 overexpression may represent an alternative mechanism to p53 mutation for escaping the p53-mediated growth control. Interestingly, multiple MDM-2 protein isoforms have been described and the possibility of functional differences between various isoforms has been raised. Previously, we demonstrated significant MDM-2 mRNA overexpression in human leukemias and suggested that MDM-2 overexpression may be a marker of aggressiveness of the disease. Polyclonal antibodies (Ab) have been generated to detect various isoforms of the MDM-2 protein. Using these Abs, we confirmed MDM-2 protein overexpression in leukemias. Furthermore, we observed heterogeneity in the isoforms expressed in various types of leukemias. In addition, we demonstrated that analysis by flow cytometry could be used as a diagnostic tool for detecting altered MDM-2 protein expression in leukemias. Here we review and expand our initial observations and confirm MDM-2 mRNA and protein overexpression by reverse transcription-polymerase chain reaction (RT-PCR), flow cytometry, and western blot analyses. Understanding the possible role of MDM-2 oncogene expression in leukemias may establish the scientific basis for new therapeutic approaches.
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PMID:Multiple patterns of MDM-2 deregulation in human leukemias: implications in leukemogenesis and prognosis. 777 50

p53 is a nuclear phosphoprotein which acts as a tumour suppressor factor, regulating cell growth and division. Mutations in the p53 gene appear to be the most common genetic alterations in human cancer. The aim of this study was to investigate p53 expression in laryngeal squamous cell carcinomas and to assess its role as a marker of prognostic significance. Using immunohistochemical staining techniques, a series of laryngeal carcinomas (n = 87) were examined for expression of the mutant form of p53 phosphoprotein using the monoclonal antibody PAB 1801. p53 over-expression was noted in 50 biopsies of laryngeal carcinomas (57.5%) but not in any of the non-neoplastic laryngeal mucosa which were used as the control. There was no statistical correlation between p53 immunoreactivity and the clinicopathological parameters of the cancers including: site of tumour, TNM staging, differentiation grading and tumour recurrence. These findings indicate that p53 expression is strongly associated with carcinoma cells and not with normal cells in the larynx. However, p53 expression is probably unrelated to the biological aggressiveness of these tumours.
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PMID:Over-expression of tumour suppressor gene p53 in laryngeal squamous cell carcinomas and its prognostic significance. 778 34

Abnormalities of the tumour suppressor gene p53 have been shown in approximately 60% of advanced gastric adenocarcinomas and it has been suggested that the immunohistochemical finding of increased p53 expression is a prognostic marker in gastric cancer. No studies of early (T1) tumours have been reported. Over expression of p53 protein in 95 early gastric carcinomas and in adjacent mucosa was investigated using immunohistochemistry with antibody CM1. Thirty five per cent of the tumours were positive. The frequency of p53 positivity in tumours of tubular histological type (46%) was significantly higher than that in signet ring tumours (10%) (p = 0.006), and neoplasms that invaded deeply into the submucosa were more frequently positive (45%) than others (30%). Five of eight (62%) T1 tumours with lymph node metastases showed immunoreactive p53. In signet ring tumours, immunopositivity correlated with the frequency of DNA aneuploidy. p53 Over expression was also found in 15% of 26 examples of high grade dysplasia in mucosa adjacent to invasive tumours. No positivity was found in intestinal metaplasia or in normal mucosa. The findings show that immunocytochemically demonstrable over expression of p53 correlates with other morphological markers of aggressiveness in T1 gastric adenocarcinoma. The increasing frequency of p53 immunoreactivity in the sequence of high grade dysplasia-->early gastric cancer-->advanced gastric cancer supports the view that abnormalities of p53 are related to tumour progression in gastric carcinogenesis.
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PMID:Expression of p53 in early (T1) gastric carcinoma and precancerous adjacent mucosa. 782 4

The expression of C-myc p62, bcl-2, p53, PCNA and EBV-encoded LMP-1 proteins was studied by immunohistochemistry on paraffin-embedded skin specimens from 14 patients with early stage (premycotic erythema and second stage plaques) mycosis fungoides (MF), 21 patients with advanced stage MF (third stage plaques and tumors), 3 patients with Sezary's syndrome (SS) and 3 patients with pleomorphic medium and large cell cutaneous T-cell lymphomas (PML-CTCL). All 41 cases were also screened for the presence of EBV by using RNA in situ hybridization with EBER 1/2 oligonucleotides. Increased expression of C-myc p62, p53 and PCNA proteins was found in PML-CTCL and advanced stages of MF as compared to early stages of MF. These results suggest a relationship between levels of C-myc p62, p53 and PCNA proteins and aggressiveness of the cutaneous T-cell lymphomas. Furthermore, C-myc p62 and bcl-2 proteins were found to be frequently coexpressed in the present series. In view of the background information from in vitro findings and animal models that cooperation of C-myc and bcl-2 is important for lymphomagenesis, our results suggest that coexpression of these oncogenes may be implicated in the pathogenesis and/or the progression of cutaneous T-cell lymphomas. Neither LMP-1 expression nor EBV EBER l/2 transcripts were detected in our series suggesting that EBV is not involved in the pathogenesis of cutaneous T-cell lymphomas.
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PMID:Mycosis fungoides: expression of C-myc p62 p53, bcl-2 and PCNA proteins and absence of association with Epstein-Barr virus. 783 Nov 52

In this study we investigated 56 renal cell carcinomas immunohistochemically for the expression of proliferating cell nuclear antigen (PCNA) and tumour suppressor protein p53. We also analyzed for the presence of human papilloma virus (HPV) DNA subtypes 6, 11, 16, 18, 31 and 33 by in situ hybridization. In carcinomas which showed more than 10% of PCNA positive nuclei there were significantly more cases with invasion (P = 0.032) or metastatic disease (P = 0.047). Nine out of 22 grade III-IV tumours (40.9%) but only six out of 30 grade I-II tumours (20%) showed more than 10% of PCNA positive cells (P = 0.097). Patients with 10% or more PCNA positive cells in kidney tumours had more advanced disease at the time of diagnosis than those showing less PCNA positive cells (P = 0.05). Six p53 positive cases were found among 56 tumours (11%), but only one case had more than 10% positive cell nuclei. The presence of HPV DNA was found in 29 out of 56 cases (52%). Multiple subtypes were found in 19 cases (34%). The most commonly occurring subtypes were 18 and 33. There was no association between PCNA, p53 and the presence of HPV DNA subtypes. Because of the association of PCNA with invasion and metastatic disease, it would be worth while to study PCNA further as a possible marker for aggressiveness of renal carcinomas. Both this study and those concentrated on mutational analysis suggest that p53 is generally not important for the development of renal cell carcinoma. On the other hand, the presence of HPV DNA in these tumours implicates HPV viral infection in the aetiology of renal cancer.
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PMID:Proliferating cell nuclear antigen but not p53 or human papillomavirus DNA correlates with advanced clinical stage in renal cell carcinoma. 783 39

Immunohistochemical analysis of the p53 tumor suppressor gene was performed in 69 human pancreatic ductal adenocarcinomas, using a highly specific anti-p53 antibody. Nuclear immunoreactivity was found in 40 tumors, yielding an overall frequency of 58%. Immunoblotting confirmed that nuclear immunoreactivity was associated with increased p53 protein levels. p53 mRNA levels were increased in 9 of 9 tested cancers, without evidence for gene amplification. Analysis of the immunostaining data by chi-square and log-rank indicated that the presence of nuclear immunoreactivity correlated with a more advanced clinical stage, and a statistically significant decrease in the post-operative survival period. In 12 cancers, metastatic tissue samples were also available for p53 analysis. Nuclear p53 immunostaining in the primary tumors was not always associated with p53 immunoreactivity in the metastatic samples, and metastases occurred in the absence of nuclear p53 immunoreactivity in the primary lesion. These findings suggest that increased p53 protein levels in human pancreatic cancer may be due not only to p53 mutations which attenuate the degradation of the protein but also to an increase in p53 mRNA levels leading to increased p53 synthesis, and that p53 nuclear immunoreactivity in these cancers implies enhanced tumor aggressiveness but is not essential for the development of metastases.
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PMID:p53 expression in human pancreatic cancer correlates with enhanced biological aggressiveness. 787 70

Sixty-nine cases of clinical Stage I non-seminomatous germ cell tumors (NSGCT) of the testis were immunostained for the protein product of the p53 tumor suppressor gene using a microwave-based antigen retrieval method. It was assumed that the immunohistochemical detection of the p53 protein corresponded to a point mutation in the p53 gene, the wild-type p53 protein turning over too rapidly to be detected by routine immunohistochemical techniques. The results of p53 staining were then compared with the results, on the same paraffin tissue blocks, of S-phase analysis, as determined by flow cytometry, and the percentage of neoplastic cells exhibiting immunohistochemical positivity for proliferating cell nuclear antigen (PCNA). Thirty-four of 69 (49%) of the clinical Stage I NSGCT exhibited p53-positivity as strong, but focal, intranuclear positivity. Both the mean total S-phase and the mean percentage of PCNA-positive neoplastic cells were significantly higher in the p53-positive cases (27.8% and 89.6%, respectively) compared with the p53-negative cases (17.6% and 66.1%, respectively). Stratification of cases into high (> or = 76%) and low categories for PCNA values correlated significantly (P < 0.0005) with p53-positivity and negativity, respectively, by chi 2 analysis. The positive association of p53 protein expression with higher proliferative indices in NSGCT of the testis is consistent with the observation of p53 mutations correlating with markers of increased tumor aggressiveness in other types of neoplasia.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The correlation of P53 protein expression with proliferative activity and occult metastases in clinical stage I non-seminomatous germ cell tumors of the testis. 790 55

There is increasing evidence that genes involved in normal cell growth and differentiation (oncogenes) or genes that encode for growth factors are important in determining the development and biologic aggressiveness of gastric carcinoma. This study was undertaken to define the prognostic value of the overexpression of p53 protein, c-erbB-2 protein, EGFr protein and PCNA in gastric carcinomas. Using monoclonal antibodies, immunohistochemical studies were performed on formalin-fixed, paraffin-embedded tissue sections from 84 primary gastric carcinomas. Overall, 34% of gastric carcinomas had nuclear-staining for p53 protein, 34% of carcinomas membrane staining for the c-erbB-2 and 74% of carcinomas membrane and cytoplasmic staining for EGFr, showing distribution in a heterogeneous fashion. PCNA was expressed as Grade 2 and 3 in 75% of patients with gastric carcinomas. Both c-erbB-2 and p53 staining was significantly associated with high grade expression of PCNA. p53 staining tended to be associated with positive nodal status and metastasis, and c-erbB-2 staining with positive nodal status only. Multivariate analysis using the Cox model showed that overexpression of p53 protein, c-erbB-2 protein and PCNA was not an independent prognostic variable in gastric carcinoma. These results suggest that expressions of p53 and c-erbB-2 protein are heterogeneous and that p53 and c-erbB-2 overexpressions are significantly associated with high proliferative activity in gastric carcinoma.
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PMID:Immunohistochemical detection of p53 protein, c-erbB-2 protein, epidermal growth factor receptor protein and proliferating cell nuclear antigen in gastric carcinoma. 791 Oct 25

A number of gene alterations have been detected in human breast cancer, and their clinicopathological implications have been investigated. Amplification of the c-erb B-2 gene and point mutations of the p53 gene are shown to be associated with biological aggressiveness of cancer cells, whereas loss of heterozygosity on chromosome 16q is suggested to be associated with acquirement of malignant phenotype. Because these gene alterations are accumulated frequently even at the preinvasive stage, the genotype as well as phenotype of breast cancer appears to have been determined mostly relatively soon after tumorigenesis.
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PMID:[Accumulation of gene alterations and progression of breast cancer]. 791

The tumor suppressor gene TP53 encodes for a nuclear phosphoprotein involved in the control of cell proliferation, particularly in stressed cells. TP53 gene mutations are the most frequent genetic event found in human cancers. Most mutations locate in the highly conserved domains of the gene. Their localizations vary according to the tissue and tumor type, but define some hot spot regions that may have a certain degree of tissue specificity. In certain cases, the type of nucleotide substitutions observed can help to find the carcinogenic agent. In recent years, TP53 gene mutations have been frequently observed in human skin tumors. In epithelial carcinomas, they involve mainly exons 5, 7, and 8. Interestingly, many are C to T transitions at dipyrimidine sites; particularly, one can find CC to TT double-base changes that are known to be specific to ultraviolet radiation. These data confirm at the molecular level the role of ultraviolet radiation as an important etiologic factor in the genesis of these lesions. The high incidence of TP53 mutations suggest that they play a role in keratinocyte transformation. Nevertheless, this event has not yet been defined as an early or late event. In melanomas, most studies have shown the detection of the p53 protein by immunohistochemistry, suggestive of the presence of a mutation in the gene prolonging the protein half-life. Anti-p53 reactivity is frequent in these tumors and seems to correlate with tumor aggressiveness. Confirmation and characterization of TP53 gene mutation at the DNA level would help to precisely define the role of this gene in the development of these tumors.
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PMID:TP53 tumor suppressor gene and skin carcinogenesis. 796 69


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