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)

Carcinogenesis in human large intestine is a result of multiple, heterogeneous and random genetic changes. Deletion of tumor suppressor genes and activation of oncogenes appear to be important molecular events. These compromise the loss of chromosomes 5, 17, 18 or functional inactivation of FAP, p53 and DCC genes. Activation of Ki-ras and c-myc oncogenes seems to be crucial for both cell immortalization and morphology modification. Identification of genes involved in this process enables both a screening and a new classification. Also it is an important step towards a gene therapy.
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PMID:Colorectal carcinoma as a genetic phenomenon. 129 35

The etiology of cancer is a complex interplay of various factors, including genetic alterations. Multiple studies have been carried out to identify and characterize mutations that frequently occur during tumorigenesis. In human breast cancer, amplification of proto-oncogenes (c-myc, c-erbB-2/neu) and chromosome 11q13, mutation of p53 and loss of heterozygosity (chromosomes 1, 3p, 6q, 7q, 11p, 13q, 16q, 17, 18q and 22q) represent the major types of genetic abnormalities that have been frequently observed in tumor DNAs. The genetic deletions and mutations could inactivate tumor-suppressor genes. In some studies, specific alterations have been associated with some clinical parameters. Recently, linkage analyses, on large families with a predisposition to breast cancer, have been performed to map putative breast cancer susceptibility genes. The survey of high risk patients should be organised to make an earlier diagnosis.
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PMID:[Molecular analysis of breast cancers: recent developments]. 130 32

When rat 3Y1 cells were infected with Rous sarcoma virus (RSV) variant SR-RSV-D(H), many 3Y1 cells acquired a stable provirus but only few of them formed transformed foci. In contrast, 12E1AY cells (3Y1 cells expressing the adenovirus type 12 [Ad12] E1A protein) formed transformed foci upon RSV infection with the same high frequency as did chicken embryo fibroblast cells. This enhancement of focus-forming efficiency was specifically observed in 3Y1 cells expressing Ad12 E1A protein but was not observed in 3Y1 cells expressing simian virus 40 T, c-myc, p53, c-fos, or v-fos protein. This enhancement was not evident in 5E1AY cells (3Y1 cells expressing the Ad5 E1A protein). Judging from the experiment using Ad12-Ad5 hybird E1A DNAs, the N-terminal half of the Ad12 E1A protein was responsible for this enhancement. The promoter activity of the RSV long terminal repeat measured by pLTR-CAT did not correlate to the efficiency of focus formation by RSV in these 3Y1 cells. Moreover, RSV containing the neo gene instead of the src gene produced G418-resistant cells equally efficiently among 3Y1, E1AY, and chicken embryo fibroblast cells. These results suggest that the enhancement of focus formation by RSV is not due to the increased expression of the src gene by the E1A protein. src mRNA and src protein were lower in RSV-transformed E1AY (RSVE1AY) cells than in RSV-transformed 3Y1 (RSV3Y1) cells. The phosphotyrosine-containing proteins were also less abundant in RSVE1AY cells than in RSV3Y1 cells, suggesting that E1AY cells require a lower threshold dose of p60v-src for transformation than do 3Y1 cells. E1AY cells were found to be more sensitive to lysis by detergents. The results suggest that the enhancement is due to changes in membrane structures in E1AY cells.
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PMID:Highly efficient focus formation by Rous sarcoma virus on adenovirus type 12 E1A-transformed rat 3Y1 cells. 131 Jul 57

Wild-type (wt) p53 has been suggested to be the product of a tumor-suppressor gene. Recently, it has been shown that the E6 oncoproteins of human papillomavirus (HPV) types 16 and 18, like the SV40 large T antigen, are physically associated with wt p53. We have investigated the functional interaction of wt p53 with the viral oncogene products of HPV16 and 18 and with cellular oncogenes by transfection of NIH3T3 cells with p53 wt alone or with several oncogene(s). We found that over-expression of HPV18 E6, c-myc or activated H-ras, like SV40 large T, can partially overcome the growth-inhibitory effect of wt p53 in NIH3T3 cells, while HPV16 E6 and E7, HPV18 E7, k-fgf, c-fos and mutant (mt) p53 do not. Further studies indicate that HPV18 E6 and c-myc can overcome the antiproliferative effect, but not the antitransforming effect, of wt p53, while activated H-ras can overcome both the antiproliferative and antitransforming effects of wt p53. These data show evidence of a functional interaction between HPV18 E6 and wt p53, and suggest that the cooperation of HPV E6 and cellular oncogenes c-myc and H-ras, which are activated in several cases of human cervical cancers, may be necessary to overcome completely the anti-oncogenic function of p53 in the development of these tumors.
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PMID:Functional interaction of p53 with HPV18 E6, c-myc and H-ras in 3T3 cells. 132 2

The data presented here indicate that the pathogenesis of AIDS-NHL is variably associated with multiple genetic alterations including monoclonal EBV infection, oncogene activation (c-myc, N-, Ki-ras) and tumor suppressor gene (p53) inactivation. Up to three (3 cases) or four (1 case) different lesions have been observed in the same tumor. The distribution of these lesions among the various histotypes is heterogeneous, although some preferential associations have been found either between lesion and histotype or between lesions. The most notable case involves p53 mutations/loss that is exclusively associated with the SNCC lymphoma subtype. Since alterations of the c-myc gene occur at very high frequency in this same histotype it is possible that both lesions may be required for the pathogenesis of the BL phenotype. The consistent negativity of p53 lesions in other NHLs associated or non associated with HIV infection (18) reinforces this hypothesis. Finally, we note that the frequency of p53 mutations is significantly higher in AIDS-BL than in non HIV-related BL (18), although the significancy of this difference remains to be assessed. This study confirms the relatively low frequency of EBV infection in systemic AIDS-NHL in general, but reinforces the notion that EBV may be required for the pathogenesis of AIDS-LC-IBP, as recently suggested by the high frequency of EBV positivity in primary CNS AIDS-NHL which are mostly represented by LC-IBP (2). Conversely, the low frequency of EBV sequences in the AIDS-SNCC lymphomas appears similar to that observed in sBL. Only in a small minority of cases were ras oncogene mutations found, mostly associated with the BL type.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Molecular pathogenesis of HIV-associated lymphomas. 132 69

Fifteen primary non-small-cell lung carcinomas (8 adenocarcinomas and 7 squamous-cell carcinomas) were analyzed by multiparameter flow cytometry for their expression of p53 and c-myc proteins. In addition, the fraction of cells staining with the proliferation-associated antibody Ki-67 and DNA ploidy was determined. These 4 biological markers were analyzed in parallel samples from a single-cell suspension made from fresh, frozen biopsies. Thus, the internal relationship between these markers within each tumor-cell population was established. Three different anti-p53 antibodies were used: PAb 421, PAb 1801 and PAb 240. All 15 tumors were p53-positive with the antibodies PAb 1801 and PAb 240, whereas only 9 were positive as judged by the antibody PAb 421. This indicates that the choice of p53 antibody is not irrelevant. Ten tumors were c-myc-positive; 7 of these were adenocarcinomas. The c-myc-positive tumors had a significantly higher level of p53 expression, judged by PAb 1801 and PAb 240, than c-myc-negative tumors. For PAb 421, there was no difference. We did not find any correlation between Ki-67 staining and expression of p53 and c-myc proteins, either with DNA ploidy, S-phase fraction or histological type. Our study indicates that there might be an association between accumulation of p53 protein and c-myc over-expression in non-small-cell lung cancer, and that this in particular might apply to adenocarcinomas. Furthermore, we show that multiparameter flow cytometry is a powerful tool in the study of the relationship between different markers in a cell population.
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PMID:Quantitation of biological tumor markers (p53, c-myc, Ki-67 and DNA ploidy) by multiparameter flow cytometry in non-small-cell lung cancer. 133 53

The expression of nine oncogenes (c-myc, N-myc, N-ras, H-ras, k-ras, abl, fos, src, and raf) and two tumor suppressor genes (p53 and RB) were studied by northern blot hybridization in six human hepatocellular carcinoma or hepatoblastoma cell lines (PLC/PRF/5, Hep3B, Hep G2, 2.2.15, HLE, and HLF) and in a human embryonic lung fibroblast cell line (WI-38) to look for differences that might be associated with the presence (PLC/PRF/5, Hep3B, and 2.2.15) or absence (Hep G2, HLE, and HLF) of integrated hepatitis B virus (HBV) DNA. The levels of expression of the oncogenes and tumor suppressor genes were unrelated to the presence or absence of integrated HBV-DNA. Furthermore, the intensity of expression of these oncogenes was no greater in the 2.2.15 cell line (consisting of Hep G2 cells transfected with hepatitis B virus) than in untransfected Hep G2 cells.
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PMID:Expression of oncogenes and tumor suppressor genes in human hepatocellular carcinoma and hepatoblastoma cell lines. 133 79

Activation of an endogenous endonuclease has been observed in conjunction with the structural changes of apoptosis in a wide variety of cell types and circumstances. The endonuclease is present constitutively in some cells (e.g. rodent cortical thymocytes) in which apoptosis is readily triggered by many unrelated stimuli, but is inducible in others. Purification of this enzyme is an objective of some importance in apoptosis research, as it might act as a marker of susceptibility to apoptosis and lead to better understanding of the regulation of the process as a whole. Early data suggest that the thymocyte endonuclease is an anionic protein of molecular weight greater than 110 kDa, with a pH optimum of 7.5 and a double-strand cleavage preference. Its activity, and the induction of apoptosis as a whole, is regulated by several familiar cellular proto-oncogenes and oncosuppressor genes, including c-myc, Ha-ras, bcl-2 and p53.
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PMID:The apoptosis endonuclease and its regulation. 133 78

The expression of the protooncogene encoded proteins (c-erbB1, c-erb B2, c-myc, c-fos) and the suppressor gene product p53 was analyzed in 81 human squamous cell carcinomas of the lung and correlated with clinical parameters of the patients (patient survival, presence of metastases and tumor stage) and with biological characteristics of the tumors (tumor growth in nude mice, DNA-ploidy, proliferative activity, drug-resistance and P-glycoprotein or gluathione S-transferase expression). By means of immunohistochemistry, expression of c-erbB1 oncoprotein (EGF-receptor) was detected in 79% of the tumors, c-erbB2 (c-neu) proteins in 35%, c-myc proteins in 48%, c-fos proteins in 41%, and p53 in 43% of the tumors. Patients with c-erbB1 positive tumors had a poor prognosis (p = 0.021). In addition, these tumors were more frequently drug resistant (p = 0.0067). A significant correlation between the growth of the squamous lung carcinomas in nude mice and c-fos oncoprotein expression was demonstrated (p = 0.017). Therefore, EGF-receptor and c-fos products may serve as prognostic factors for the aggressiveness of squamous cell carcinomas of the lung and for the response of these tumors to chemotherapy. No significant correlation was found between the expression of the c-erbB1 or c-fos gene products and stage, metastasis and DNA-ploidy. In contrast to these results, no relationship was found between c-neu or c-myc gene products expression and any of the clinical or biological parameters examined. Aneuploid squamous cell carcinomas of the lung expressed p53 more frequently than diploid tumors (p = 0.027). However, there was no significant difference between p53 expression and stage, survival of patients, metastasis, growth of the tumors in nude mice, proliferative activity and drug-resistance of the tumors.
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PMID:Oncoprotein (c-myc, c-erbB1, c-erbB2, c-fos) and suppressor gene product (p53) expression in squamous cell carcinomas of the lung. Clinical and biological correlations. 134 20

Castration initiates extensive apoptosis of the secretory epithelial cells lining the ducts of the rat ventral prostate, resulting in the striking regression of this male sexual accessory tissue. We had previously described the paradox of finding similar cascades of gene activity (c-fos greater than c-myc greater than hsp-70) induced during the early period of ventral prostate regression and during the regrowth of the ventral prostate gland initiated by testosterone replenishment. This common pattern of protooncogene expression during periods of predominant cellular apoptosis or proliferation caused us to examine further the possibility that the two cellular events occur through identical early molecular pathways. In the present study we demonstrate that apoptotic prostate epithelial cells incorporate bromodeoxyuridine into nuclear high-molecular-weight DNA prior to nuclear DNA fragmentation. The DNA synthetic activity occurs in coordination with a massive induction of proliferative cell nuclear antigen, a proliferation marker, in the nuclei of androgen-deprived prostatic epithelial cells. Moreover, this activity is also associated with the increased expression of mRNA encoding p53, a suppressor gene well known as a cell cycle-blocking agent. Our data indicate that quiescent (G0) prostate epithelial cells undergo apoptosis due to two sequential events initiated by testosterone depletion. The first event is the active reentry of these cells into the cell cycle. The second event is the apoptotic destruction resulting from the inability of the differentiated cells to successfully complete this cycle.
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PMID:Hormone-regulated apoptosis results from reentry of differentiated prostate cells onto a defective cell cycle. 135 2


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