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 effects of sodium butyrate on simian virus 40 early gene expression were determined in SV40-transformed human embryonic lung fibroblasts (SVWI-38). Northern blot analysis and nuclear run-off transcription studies revealed that treatment of cells with millimolar concentrations of sodium butyrate (2.5 to 10 mM) resulted in increased levels of SV40 early gene transcripts, with a concomitant increase in their corresponding proteins (large-T and small-t antigens). Although sodium butyrate treatment enhanced the expression of the early genes, it was associated with a reduction in cell growth and total protein synthesis, as measured by cell number and incorporation of 3H-leucine into macromolecules, respectively. Immunoprecipitation of 35S-labelled cellular proteins with anti-p53 and anti-T antibodies revealed that the level of the cellular protein, p53, declined markedly in the presence of sodium butyrate. Furthermore, in control cells only 30% of the p53 was complexed with large-T antigen, whereas in butyrate-treated cells all the p53 was complexed with large-T antigen. The increased early gene expression was not due to altered methylation patterns, gene amplification, or rearrangement of the integrated SV40 genome. Sodium butyrate treatment did, however, result in the appearance of a new nuclear protein which bound specifically to a SV40 promoter fragment containing large-T antigen binding sites I and II.
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PMID:Elevation of large-T antigen production by sodium butyrate treatment of SV40-transformed WI-38 fibroblasts. 132 17

Immunolocalization of the nuclear protein p53 tumor suppressor gene product is considered to be one of the best methods of detecting a mutated form of p53. We have studied p53 immunohistochemically by using monoclonal antibody pAb1801 in 15 cases of esophageal squamous cell carcinoma. Immunoreactive p53 was observed in the nuclei of tumor cells in 4% paraformaldehyde-fixed, frozen sections (12 of 15) and paraffin-embedded sections (11 of 15), but not in routinely processed (10% formalin-fixed) specimens. p53 expression was closely correlated with the malignant phenotype, including dysplasia. p53 was not observed in histologically normal mucosa, except in three cases in which scattered immunoreactivity was observed in parabasal and basal cells. Immunostaining of ki67 and proliferating cellular nuclear antigen on adjacent tissue sections revealed that p53 expression was strongly correlated with ki67 and proliferating cellular nuclear antigen in carcinoma and dysplastic cells, but not in normal mucosa, suggesting involvement of the mutated form of p53 in the cell cycle of malignant cells. Immunohistochemical patterns of p53 were not related significantly to clinicopathologic parameters in the cases examined. Therefore, p53 expression was strongly associated with the proliferation of carcinoma cells but not with that of normal cells in esophageal carcinoma.
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PMID:Expression of p53 in human esophageal carcinoma: an immunohistochemical study with correlation to proliferating cell nuclear antigen expression. 135 81

P53 is a tumour suppressor gene, located in the short arm of chromosome 17, which encodes for a nuclear protein involved in the control of cellular growth, regulating the entry of the cell into the S-phase. P53 mutations have been identified in a progressively increasing number of human malignancies. Nuclear p53 protein is usually present in non-tumour cells in minute concentrations, due to its short half-life. In contrast, tumours with p53 mRNA mutations show a higher nuclear protein concentration, detectable by immunohistological techniques, due to stabilization by complexing with other proteins such as heat-shock protein or wild-type p53 protein. Levels of nuclear p53 protein detected by immunohistochemistry with the monoclonal antibody PAb 1801 were measured with the aid of an image analysis system in 83 non-Hodgkin's lymphomas (NHLs) and 13 cases of Hodgkin's disease, as well as in 14 cases of normal thymus, reactive tonsils, and lymphadenitis. High levels of p53 protein (greater than 5 per cent of the cells) were present only in high-grade lymphomas (in the proportion 13/55), with a peak incidence in Burkitt's lymphoma (5/8 cases). Lower levels (less than 5 per cent) of p53 protein were detected in low-grade B- and T-cell lymphomas, as well as in most of the cases of Hodgkin's disease, where p53 protein was selectively present in Hodgkin and Reed-Sternberg cells. In 5/14 reactive tonsils or lymph nodes, occasional p53-positive cells were identified. These results suggest a relationship between levels of p53 protein and the aggressiveness of NHL.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:P53 protein expression in lymphomas and reactive lymphoid tissue. 138 24

Allelic losses on the short arm of chromosome 17 occur frequently in colorectal cancers. Despite the existence of other common molecular events such as loss of the long arms of chromosomes 18 and 5, it has been demonstrated that the former has the greatest prognostic significance. Of the various genes mapping to the commonly deleted sequence, the best candidate as a 'target' seems to be the p53 antioncogene. We applied our methods of detection of the p53 protein in a series of 78 colorectal cancers stored in a tumour bank from 1985 to 1989, for which the median follow-up was 42 months. Nuclear-attached p53 was quantified by flow cytometry and soluble p53 was assayed by ELISA. Both assays used a monoclonal antibody considered to be specific for a conformational epitope present only on the mutated protein. Fifty of the 78 tumours (64%) were found to present significant levels of p53 attached to the nucleus. A further two tumours contained high levels of p53 only in their soluble fraction. Thus, 52 out of 78 cancers (67%) were considered to be positive for p53. The p53 content correlated with 17p loss (P < 0.002), hyperdiploid DNA content (P < 0.001) and tumour site (P < 0.03), but not Dukes' stage (P = 0.15). p53 negative cases had a better overall survival than p53 positive ones (P < 0.03). When the 14 stage D tumours were excluded from the analysis, p53 was no longer significantly predictive of survival (P < 0.07), but remained predictive of recurrence (P < 0.02) and metastasis (P < 0.03). Multivariate analysis was not performed because of the small number of cases. Overall, disease-free and metastasis-free survival were compared to the positivity obtained either with pAb 421 and/or 1801 or pAb 240 since all three were used in the flow cytometric analysis, defining subsets of 421-, 1801+ and 421-, 1801-, 240+. The presence of nuclear protein presenting the mutation-specific epitope, recognised by pAb 240, was found to be the most discriminant. It must be noted that univariate survival analysis demonstrated that more than 80% of patients with p53-negative tumours were alive at 3 years vs less than 50% in the p53-positive group. A large prospective study should be conducted to define the exact prognostic significance of the p53 content of colorectal carcinomas.
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PMID:Increased p53 protein content of colorectal tumours correlates with poor survival. 141 18

The tumour suppressor gene p53, located on the short arm of chromosome 17, encodes for a nuclear protein which regulates cell proliferation by inhibiting cells entering S-phase. p53 mutations are alleged to be the commonest genetic abnormality in human cancer. We studied mutant p53 oncoprotein expression, using PAb1801 monoclonal antibody immunohistochemistry, in 25 'ideal' keratoacanthomas and 26 well-, 19 moderately and 18 poorly differentiated squamous cell carcinomas of the skin. While there was a highly significant trend in the proportion of p53 oncoprotein-positive lesions from keratoacanthomas to poorly differentiated squamous cell carcinomas (chi 2 = 17.13, df = 1, exact P = 0.00003), p53 expression was inadequate for distinguishing keratoacanthoma from well-differentiated squamous cell carcinoma (chi 2 = 2.55, df = 1, exact P = 0.18; corresponding to a sensitivity of 0.84 and a specificity of only 0.36).
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PMID:Mutant p53 oncogene expression in keratoacanthoma and squamous cell carcinoma. 833 63

Mutation of the p53 gene is a key element in the development of several human cancers. Intron 4, a noncoding region of the p53 gene, is required for optimal expression of that gene. We have previously shown that nuclear protein binds intron 4 and have defined the protein-binding site. In this paper we address the question, "Does the mutant p53 gene's ability to transform cells to the malignant phenotype depend on protein binding to intron 4?" Using an in vitro assay in which the mutant p53 gene and Ha-ras oncogene cooperate in transformation of cells to the malignant phenotype, we determined the ability of mutant mouse p53 gene constructs, with and without two base pair substitutions at the intron 4 protein-binding site, to participate in malignant transformation. On Day 1, 5 x 10(5) rat embryo fibroblasts were transfected by the calcium phosphate procedure with 10 micrograms of both a mutant p53 gene construct and Ha-ras oncogene. Malignant transformation was evidenced by the formation of discrete foci of heaped-up cells. After 14 days of incubation at 37 degrees C in DMEM and 10% fetal calf serum (8% CO2), the cells were stained with cresyl violet and the foci counted. In three separate experiments, the presence of two base pair substitutions at the intron 4 protein-binding site caused a significant decrease in the number of foci formed (P less than 0.05).
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PMID:Inhibition of the mutant p53 gene in transformation assays. 159 78

Immunohistochemical analysis of p53, a nuclear protein involved in the development of numerous human tumors, was performed in a series of 50 primary nonsmall cell lung carcinomas and in a group of eight lung carcinoma cell lines. Using two mouse monoclonal antibodies, PAb1801 and PAb421, sixteen of thirty-five (45.7%) lung adenocarcinomas and seven of fifteen (46.6%) squamous cell carcinomas showed marked-to-moderate immunoreactivity. In fifty-six percent of the positive tumors more than 40% of all cells were p53 positive, and in only 17% of positive tumors the percentage of immunostained cells was less than ten. Although the number of p53 negative adenocarcinomas without metastasis was larger than the number of p53 positive tumors without metastasis, there were not clear differences between p53 positive and negative tumors with metastasis. Furthermore, six adenocarcinomas that infiltrated the pleura and/or the thoracic wall were p53 positive, whereas only two of these invasive tumors were p53 negative. From eight cell lines studied, six were positive for p53. A good correlation between immunocytochemistry and immunoprecipitation was observed. Two tumorigenic and metastatic cell lines, Calu 1 and Calu 6, that were not immunoreactive also showed lack of protein by immunoprecipitation, as well as absence of mRNA in Northern analysis. In addition, Calu 1 showed an important gene deletion. These observations point to the fact that deletions and alterations in transcription of the p53 gene could coincide with or eventuate in an advanced malignant phenotype that nevertheless results in a p53 negative immunostain. Although this type of change cannot be detected immunohistochemically in primary tumors without further molecular analysis, the results presented herein indicate that p53 can be detected immunohistochemically in a majority of lung tumors and that there is a tendency for more advanced adenocarcinoma stages to exhibit positive p53 immunostain.
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PMID:Detection of p53 in primary lung tumors and nonsmall cell lung carcinoma cell lines. 165 62

The p53 gene is a frequent target of mutation in a wide variety of human cancers. Previously, it was reported that conditional expression of wild-type p53 protein in a cell line (GM47.23) derived from a human glioblastoma multiform tumor had a negative effect on cell proliferation. We have now investigated the effect that induction of wild-type p53 protein in this cell line has on the expression of the proliferating-cell nuclear antigen gene. The proliferating-cell nuclear antigen gene encodes a nuclear protein that is an auxiliary factor of DNA polymerase delta and part of the DNA replication machinery of the cell. We show that inhibition of cell cycle progression into S-phase after induction of wild-type p53 protein is accompanied by selective down-regulation of proliferating-cell nuclear antigen mRNA and protein expression.
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PMID:Growth suppression induced by wild-type p53 protein is accompanied by selective down-regulation of proliferating-cell nuclear antigen expression. 170 14

p53 is a nuclear protein believed to play an important role, through mutation and overexpression, in the progression of human malignant tumors. The authors employed a monoclonal antibody, 1801, and investigated overexpression of p53 in a series of 255 malignant and benign tumors, using deparaffinized sections of methacarn-fixed tissue. Overall, immunohistochemically detected p53 overexpression was found in 39% of malignant tumors, with considerable variation within individual tumor types (34% of breast carcinomas, 92% of ovarian carcinomas, 33% of soft tissue sarcomas). Homogenous, heterogenous, and focal immunostaining patterns were noted. With rare exceptions, no immunostaining of any benign tumors was noted. No immunostaining was found in adjacent, benign tissues, or in a series of fetal tissues. This is the first demonstration of widespread p53 overexpression in alcohol-fixed, embedded tissue and confirms the major role played by p53 in human malignancies.
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PMID:Widespread p53 overexpression in human malignant tumors. An immunohistochemical study using methacarn-fixed, embedded tissue. 173 21

The nuclear protein p53 has been measured in archival lung cancer biopsies. The monoclonal antibody PAb 1801, which recognizes human p53, was used. After immunostaining, the nuclei prepared from paraffin-embedded tissue were stained with propidium iodide for simultaneous measurement of DNA content; 17 of 24 lung cancers were p53 positive. The S-phase fraction in positive tumors was 22.9 +/- 6.4%, as compared to 13.6 +/- 6.1% in negative tumors (P less than 0.02). In ten of the positive tumors (two small cell carcinomas and eight non-small cell carcinomas), the p53 expression varied through cell cycle, whereas in seven tumors (five small cell carcinomas and two non-small cell carcinomas), no such variation of p53 expression was observed. Freezing the nuclear suspensions did not substantially reduce the p53 signals. Control experiments with the SV40-transformed human foreskin fibroblast cell line HSF4-T12 showed that the enzymatic digestion utilized to dissociate paraffin-embedded tissue did not significantly reduce p53 fluorescence. Immunohistochemical staining of biopsy specimens indicated that only cancer cells were overexpressing p53. In conclusion, using the monoclonal antibody PAb 1801, p53 is detectable in cell nuclei prepared from paraffin-embedded bronchial carcinoma biopsies. P53 positive tumors have increased proliferative activity compared to p53 negative tumors. Furthermore, the lack of cell cycle variation of p53 in small cell carcinomas indicates that this pattern may be related to high-grade malignancy.
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PMID:Flow cytometric measurement of p53 protein expression and DNA content in paraffin-embedded tissue from bronchial carcinomas. 193 58


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