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)

To study the importance of estradiol concentrations in which tumors are growing to progression of tumor growth and cell kinetics, we have used a human tumor-nude mice model. In this model a human endometrial adenocarcinoma with estradiol independent but estradiol-responsive growth phenotype (i.e. the tumor was capable of growing in absence of estradiol but its growth could be stimulated by estradiol at the start of preparation phase) was examined. In the preparation phase pieces from this tumor were transplanted into nude mice, randomly divided into two groups, one with and one without estradiol treatment. After 18 months growth in these different hormone conditions the tumors were measured for p53 protein expression and pieces from both these groups were again transplanted into oophorectomized nude mice, each group being randomly allocated to two subgroups, one with and one without estradiol treatment (experimental phase). Tumor growth was measured during the experimental phase, whereas cell kinetic parameters and steroid receptor concentrations were analyzed after the experimental phase. Our findings indicate that progression of the growth phenotype is independent of estradiol conditions in which human endometrial adenocarcinomas are grown. Long-term growth in estradiol-poor conditions results in estradiol resistance of the cell cycle, probably accompanied by overexpression of the p53 protein. Tumor growth in estradiol-rich conditions, however, may protect, at least to some extent, the same tumor, which retains higher sensitivity of cell proliferation to estradiol and normal production of the p53 protein despite progressive changes in growth regulation.
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PMID:Effect of estradiol on tumor growth, cell kinetics and p53 oncoprotein expression in human endometrial adenocarcinoma heterotransplanted into nude mice. 811 Sep 90

The tumor growth suppressor WAF1/CIP1 was recently shown to be induced by p53 and to be a potent inhibitor of cyclin-dependent kinases. In the present studies, we sought to determine the relationship between the expression of WAF1/CIP1 and endogenous regulation of p53 function. WAF1/CIP1 protein was first localized to the nucleus of cells containing wild-type p53 and undergoing G1 arrest. WAF1/CIP1 was induced in wild-type p53-containing cells by exposure to DNA damaging agents, but not in mutant p53-containing cells. The induction of WAF1/CIP1 protein occurred in cells undergoing either p53-associated G1 arrest or apoptosis but not in cells induced to arrest in G1 or to undergo apoptosis through p53-independent mechanisms. DNA damage led to increased levels of WAF1/CIP1 in cyclin E-containing complexes and to an associated decrease in cyclin-dependent kinase activity. These results support the idea that WAF1/CIP1 is a critical downstream effector in the p53-specific pathway of growth control in mammalian cells.
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PMID:WAF1/CIP1 is induced in p53-mediated G1 arrest and apoptosis. 811 1

p53-deficient mouse embryonic fibroblasts were used to establish a direct mechanism of tumor suppression by p53 involving the destruction of oncogene-expressing cells by apoptosis. The absence of p53 enhanced cell growth, appeared sufficient for immortalization, and allowed a single oncogene [adenovirus early region 1A (E1A)] to transform cells to a tumorigenic state. p53 suppressed transformation of E1A-expressing cells by apoptosis. Apoptosis was associated with p53 stabilization and was triggered by environmental signals that normally suppress cell growth. Absence of even a single p53 allele significantly enhanced cell growth and survival. Although abrogation of apoptosis allowed transformation by E1A alone, escape from apoptosis susceptibility was not a prerequisite for tumor growth. Consequently, p53 mutation could enhance the survival of malignant cells expressing oncogenes activated early in tumor progression.
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PMID:Abrogation of oncogene-associated apoptosis allows transformation of p53-deficient cells. 813 44

The ability of simian virus 40-encoded large T antigen to disrupt the growth control of a variety of cell types is related to its ability to interfere with certain cellular proteins, such as p53 and the retinoblastoma susceptibility gene product (pRB). We have used wild-type and mutant forms of T antigen in transgenic mice to dissect the roles of pRB, p53, and other cellular proteins in tumorigenesis of different cell types. In this study, using a cell-specific promoter to target expression specifically to brain epithelium (the choroid plexus) and to B and T lymphoid cells, we characterize the tumorigenic capacity of a T-antigen fragment that comprises only the amino-terminal 121 residues. This fragment (dl1137) retains the ability to interact with pRB and p107 but lacks the p53-binding domain. While loss of the p53-binding region results in loss of the capacity to induce lymphoid abnormalities, dl1137 retains the ability to induce choroid plexus tumors that are histologically indistinguishable from those induced by wild-type T antigen. Tumors induced by dl1137 develop much more slowly, however, reaching an end point at around 8 months of age rather than at 1 to 2 months. Analysis of tumor progression indicates that tumor induction by dl1137 does not require secondary genetic or epigenetic events. Rather, the tumor growth rate is significantly slowed, indicating that the T-antigen C-terminal region contributes to tumor progression in this cell type. In contrast, the pRB-binding region appears essential for tumorigenesis as mutation of residue 107, known to disrupt pRB and p107 binding to wild-type T antigen, abolishes the ability of the dl1137 protein to induce growth abnormalities in the brain.
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PMID:Induction versus progression of brain tumor development: differential functions for the pRB- and p53-targeting domains of simian virus 40 T antigen. 813 68

The mutation of tumor suppressor genes is thought to contribute to tumor growth by inactivating proteins that normally act to limit cell proliferation. Several tumor suppressor proteins have been identified in recent years, but only two of them, p53 and pRb, are understood in detail. In the past year, a role has become apparent for both of these proteins in transcription and phosphorylation events required for passage of a cell from G1 to S phase. The pRb protein appears to prevent the function of transcription factors and other proteins needed for S phase until its inactivation by cyclin-dependent kinases in late G1. Induction of p53 by DNA damage may act to cause cell cycle arrest or cell death by altering the transcription program of damaged cells. A detailed molecular understanding of these growth regulators is now emerging, and is the subject of this review.
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PMID:Tumor suppressor genes. 819 33

The ability of p53 to activate transcription from specific sequences suggests that genes induced by p53 may mediate its biological role as a tumor suppressor. Using a subtractive hybridization approach, we identified a gene, named WAF1, whose induction was associated with wild-type but not mutant p53 gene expression in a human brain tumor cell line. The WAF1 gene was localized to chromosome 6p21.2, and its sequence, structure, and activation by p53 was conserved in rodents. Introduction of WAF1 cDNA suppressed the growth of human brain, lung, and colon tumor cells in culture. Using a yeast enhancer trap, a p53-binding site was identified 2.4 kb upstream of WAF1 coding sequences. The WAF1 promoter, including this p53-binding site, conferred p53-dependent inducibility upon a heterologous reporter gene. These studies define a gene whose expression is directly induced by p53 and that could be an important mediator of p53-dependent tumor growth suppression.
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PMID:WAF1, a potential mediator of p53 tumor suppression. 824 52

Hepatocellular carcinoma (HCC) accumulates a mutation of the p53 gene with a common substitution of nucleotide in a particular site. It is hypothesized that infection of hepatitis B virus (HBV) or exposure to aflatoxins could induce it. In Japan, the concentration of aflatoxins in the environment is low; however, infection of HBV and/or hepatitis C virus (HCV) is frequently seen in patients with HCC. The purpose of our studies was to determine whether these hepatoviral factors influence p53 alterations. In our results, p53 abnormalities, which were composed of loss of heterozygosity (LOH) and/or point mutation, were shown in 39% of patients. We postulated that they occurred at late stages in tumor growth based on the following two results. LOH analysis on p53 showed that most of the tumor nodule consisted of two phenotypes, LOH and non-LOH cancer cells. The p53 abnormalities correlated with the grade of cancer cell atypia which advanced with tumor growth. HBV and HCV infections were identified by polymerase chain reaction using DNA extracted from cancerous and noncancerous regions of the liver. By these methods, the patients who had been infected with either HBV or HCV showed an incidence of p53 abnormalities (45%) higher than those infected by neither (13%). However, the detection rate of these viruses was lower in the HCC region (33%) than that in the noncancerous region (56%) in cases with mutated p53. The low rate of HCV detection (22%) in the HCC region with altered p53 was attributable to these different viral detection rates. There was a difference in pattern of p53 mutational changes in patients depending upon whether they were infected by HBV or by HCV. Two of three HBV-infected patients had a transversional change of nucleotide at the G:C site to T:A. However, in cases with HCV, four of eight patients had a transitional change of nucleotide of p53. These results showed that HBV and HCV infections affect carcinogenic pathways causing p53 abnormalities independently.
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PMID:p53 gene abnormalities are closely related to hepatoviral infections and occur at a late stage of hepatocarcinogenesis. 826 44

Findings from molecular genetic and cytogenetic investigations suggest that mutations in suppressor genes play a key role in osteosarcoma pathogenesis. RB and p53 are frequently involved and are speculated to be indispensable components. Alterations in putative suppressor genes on chromosomes 18q and 3q additionally may be involved in various patterns. The high resolution of magnetic resonance imaging in osteosarcoma imaging is confirmed, and the validity of dynamic gadolinium-enhanced imaging for estimation of tumor response is stated. The efficacy of single-drug high-dose methotrexate convincingly is shown to be 19%. Phase II trials with nonspecific immunostimulation using a synthetic liposomal mycobacterium-derived antigen (liposomal muramyl tripeptide phosphatidylethanolamine) do not yet allow us to draw conclusions on eventual efficacy. A novel and promising approach may be intervention in the endocrine or orthocrine and paracrine tumor growth regulation. Hypophysectomy in mice dramatically reduced plasma or insulin-like growth factor and local as well as systemic growth of transplanted osteosarcoma. The close interrelation between tumor response, surgical margins, and local control is demonstrated, as well as the fatal prognosis after local failure. Also, the validity of known risk factors in patients undergoing intensive chemotherapy has been confirmed. Interestingly, dose intensity was not found to influence prognosis.
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PMID:Osteosarcoma. 836 83

The wild-type p53 gene product is a nuclear phosphoprotein that suppresses cell and tumor growth. Mutations of the p53 gene are by now the most frequently recognized genetic alterations in human malignancies and occur in many types of carcinomas as well as in astrocytomas and sarcomas. Wild-type p53 protein has a short half-life, is present in very low quantities in normal cells and cannot be detected immunohistochemically. Mutant p53 proteins have longer half-lives and are usually present in immunohistologically detectable amounts. It is generally agreed that the presence of p53 immunostaining indicates the presence of an abnormal p53 protein and is strongly suggestive of a mutation in the p53 gene. In this study, we stained paraffin sections from eight samples of gliosarcomas from seven patients with an antibody to p53. All tumors contained p53-immunoreactive nuclei in both the glial and the sarcomatous component. In five tumors, a majority of nuclei was positive in the sarcomatous component while only a minority of nuclei was positive in the glial areas. In one tumor, the reverse was seen. In another tumor, approximately half the nuclei were positive in both components and in one tumor, only a minority of nuclei were positive in either component (this lesion was the recurrence of a tumor in which the majority of the sarcoma's nuclei had been positive). These data indicate that p53 mutations may play a role in the pathogenesis of gliosarcomas and suggest an origin of both the glial and sarcomatous components from a common progenitor.
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PMID:Distribution of p53 protein expression in gliosarcomas: an immunohistochemical study. 838 97

A total of 471 cases of colonic adenocarcinomas and 28 cases of colonic adenomas were examined immunohistochemically to evaluate the expression of p53 protein in the light of their relationship with various prognostic factors. A monoclonal antibody, p53 DO-7, was used in the study. Two hundred and fourteen adenocarcinomas (45.5%) showed positive staining for p53, however only three of the adenomas (10.3%) were positive (P < 0.05). p53 was stained to neoplastic nuclei. Adjacent normal mucosal cells were negative. There were no significant correlations between p53 expression and prognostic parameters such as age, sex, gross configuration, modified Astler-Coller stages, microscopic tumor growth patterns, tumor depth, tumor size and lymph node involvements. However, left sided adenocarcinomas (49.3%) expressed p53 more often than right sided adenocarcinomas (35.6%) (P = 0.01). The positive rates were different according to the histologic differentiation; 45.2% in well differentiated, 51.3% in moderately well differentiated, 23.8% in poorly differentiated, and 26.5% in mucinous carcinomas (P = 0.011). The mean survival periods of the p53 positive and negative groups were 29 months and 32 months, respectively (P = 0.385). However, overall survival for patients with grade one and two positive p53 was better than those of grade three and four positive cases (P = 0.028). In conclusion, the result of this multivariate analysis suggests that immunohistochemically strong p53 protein expression (more than 30% of tumor cells) has value in estimating a prognosis for patients with colorectal adenocarcinomas.
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PMID:An immunohistochemical study of the expression of p53 protein in colon cancer. 852 43


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