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)

Current basic research on tumorigenesis suggests that the accumulation of multiple genetic defects underlies the progression of initiated cells toward malignancy. Molecular abnormalities associated with primary brain tumors include a wide variety of changes in tumor-suppressor genes, proto-oncogenes and growth factors. A well-known tumor-suppressor gene, p53 gene, is located on the short arm (p) of chromosome 17 and consists of 11 exons transcribed into a 2.2-2.5 kb messenger (m) RNA that encode for a 53 kDa protein. Its alterations are associated with carcinogenesis of astrocytic tumors. Recent evidence suggests also that the p53 protein may function through promoting the expression of the recently discovered gene, WAF1/Cipl. Loss of chromosome 10 was frequently observed in glioblastoma. Southern blot analysis of glioblastomas revealed that 72% have the chromosome 10 loss and that 38% had amplification of the epidermal growth factor receptor (EGFR) gene. Autocrine stimulation of cell growth requires the presence of both growth factors and their receptors. Other genetic alterations in gliomas include elevated expression of the c-myc, Ha-ras, and c-fos oncogenes with a trend to increase in higher malignant grades.
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PMID:Molecular changes involved in the carcinogenesis of brain tumors. 788 30

Non-small lung cancer (NSCLC) is a disease that exhibits multiple genetic lesions. Lung Cancer Study Group (LCSG) 871 was designed to analyze this group of malignancies for alterations in growth factors and/or their receptors, oncogenes, tumor suppressor genes, and immediate early transcription factor genes. Immunohistochemical analysis showed that 32% of evaluable cases studied contained absent or abnormal Rb expression. Sequence analysis of the p53 gene revealed that 58% of these cancers contained structural alterations of this gene, whereas only 45% of these cases overexpressed p53 by immunohistochemical analysis. Finally, both Northern blot and immunohistochemical analysis showed that these tumors exhibited changes in the mRNA and protein expression levels respectively of the immediate early transcription factor genes c-fos, c-jun, and EGR, in that less expression of these genes was evident in the tumors compared with adjacent normal tissue. Understanding both the biologic and molecular significance of these findings may allow us to explore novel modalities for treatment of this disease.
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PMID:Tumor suppressor and immediate early transcription factor genes in non-small cell lung cancer. 798 67

The E6 and the E7 genes of the high-risk types of human papillomavirus (types 16 and 18) are associated with the induction or maintenance of malignant growth. The molecular mechanism by which these oncogenes contribute to the malignant phenotype is not clear. To study the effects of E7 on cellular processes, we constructed a stable cell line that inducibly expressed the E7 gene of HPV16. By using this cell line, we provide evidence that expression of E7 of HPV16 stimulates c-fos gene expression. Also, by doing transient transfection experiments, we show that the expression of either E6 or E7 induces transcription from the c-fos promoter. Analysis of a series of c-fos promoter mutants indicates that the activation by both E6 and E7 is dependent on the cyclic AMP response element. To further investigate the mechanism(s) of the activation of the c-fos gene and their relation to the oncogenic properties of E6 and E7, several mutants of the E6 and E7 genes were analyzed. The results of these studies indicate that the CR1 and CR2 regions in the E7 protein, and sequences distinct from the p53-binding region in the E6 protein, are critical for activation of the c-fos promoter.
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PMID:Activation of the c-fos gene by the HPV16 oncoproteins depends upon the cAMP-response element at -60. 803 92

Previous studies have demonstrated that androgen responsive human prostate cancer cells can be induced to undergo programmed cell death after androgen ablation. By contrast, androgen-independent human prostate cancer cells do not activate this apoptotic pathway in response to androgen ablation. In the present study, two androgen-independent human prostatic cell lines, PC-3 and DU-145, were used as in vitro model systems to investigate the possibility of induction of programmed cell death in response to non-androgen ablative cytotoxic drugs. Treatment of these cells with the fluorinated pyrimidines, 5-fluoro-2-deoxyuridine or trifluorothymidine, resulted in a significant decrease in cell viability, over a period of 96 hr of exposure to the drugs, as determined by the trypan blue exclusion assay. The characteristic DNA fragmentation into a nucleosomal ladder and induction of expression of specific apoptosis-related genes, such as TRPM-2/SGP-2, and TGF-beta 1, but not the growth-related genes, c-myc, c-fos, and p53, temporally correlated with activation of apoptotic cell death in both systems. Simultaneous treatment with exogenous thymidine completely abrogated the fluoropyrimidine-induced cytotoxic effect in both cell lines, as well as the nucleosomal fragmentation of DNA, indicating that this apoptotic process is due to the induction of "thymineless" state. These results suggest that androgen-independent human prostate cancer cells retain the ability to activate the apoptotic cascade, after treatment with cytotoxic drugs that induce a "thymineless" state.
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PMID:Induction of apoptosis in androgen-independent human prostate cancer cells undergoing thymineless death. 803 80

A series of changes in the genes that control hepatocyte growth, or interference with the protein products of these genes, appears to have an important role in the etiology of hepatocellular carcinoma (HCC). Mutations of the p53 tumor suppressor gene have been identified in 30-50% of HCC patients in some geographic areas. Abnormalities of the RB tumor suppressor gene have been found in 20-25% of HCCs, including 80-86% of HCCs with p53 mutations. Overexpression of transforming growth factor alpha (TGF-alpha), insulin-like growth factor II (IGF-II), and the oncogenes N-ras, c-myc, and c-fos have been found in high percentages of HCC patients. The cumulative effect of these changes may be more important than the order in which they occur. Some of these changes may explain the mechanism(s) by which the hepatitis B virus participates in the development of HCC.
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PMID:Tumor suppressor genes, growth factor genes, and oncogenes in hepatitis B virus-associated hepatocellular carcinoma. 804 25

Calcium enhances keratinocyte differentiation, and 1,25 dihydroxyvitamin D3 (1,25(OH)2D3) is both antiproliferative and prodifferentiative in many cell types, including normal human keratinocytes. In the present study, we examined the combined effects of calcium and 1,25(OH)2D3 on parameters of growth and differentiation and on c-fos and p53 gene expression in normal human keratinocytes. Exposure of normal human keratinocytes to 1,25(OH)2D3 markedly reduced [3H] thymidine incorporation and cell number at low and high medium Ca++ concentrations. Simultaneously, cells in the G0/G1 phase of the cell cycle increased significantly and those in the S phase fell precipitously. 1,25(OH)2D3 and calcium also induced keratinocyte differentiation independently, as assessed by immunocytochemistry and by induction of involucrin mRNA. Both Ca++ and 1,25(OH)2D3 were shown, by nuclear run-on assays, to increase involucrin gene transcription. A rapid, transient elevation in c-fos protooncogene expression preceded these effects when epidermal growth factor was present alone. When 1,25(OH)2D3 was added to quiescent keratinocytes, there was a marked augmentation of c-fos mRNA accumulation at low and high medium Ca++ concentrations. Varying medium Ca++ concentrations had no effect on c-fos mRNA levels. Increasing medium Ca++ concentrations from 0.15 to 2.0 mM produced marked elevations of p53 mRNA accumulation and of the rate of p53 gene transcription, whereas 1,25(OH)2D3 had no effect. These results, therefore, suggest that 1,25(OH)2D3 and calcium act in concert to modulate the expression of two important cell-cycle-associated genes, which may be important components in the initial programming of growth and differentiation of normal human keratinocytes.
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PMID:Effect of 1,25 dihydroxyvitamin D3 and calcium on growth and differentiation and on c-fos and p53 gene expression in normal human keratinocytes. 807 97

Expression of cellular oncogenes in 3 lymphoid cell lines, BTL-PC3 (BoCD2-, BoCD4-, BoCD8-, BoWC1+), BLS1 (BoCD2+, BoCD4-, BoCD8-, BoWC1+) and BLT2 (BoCD2-, BoCD4-, BoCD8-, BoWC1-), which have been established from calf, skin, and thymic types of lymphosarcomas, respectively, were analyzed by DNA-RNA (northern blot) hybridization. To determine specific expression of oncogenes involved in malignant transformation of the lymphoid cells, cellular RNA was isolated from bovine tumor cell lines, BTL-PC3, BLS1, and BLT2, and from Madin Darby bovine kidney cells used as a control for bovine cell lines. The RNA was hybridized against 5 viral oncogene probes (v-jun, v-myc, v-erbB, v-erbA and v-fes), 6 human cellular oncogene probes (N-ras, c-Blym-1 c-erbB-2, c-fos, c-myb and c-abl), human p53 tumor suppressor gene, and bovine LDH-A gene probes. Line BTL-PC3 expressed 2.4-kilobase (kb) c-myc and 4.0- and 3.6-kb c-myb transcripts, and line BLT2 expressed a 3.8-kb c-myb transcript, but line BLS1 expressed no message for the oncogenes tested. Specific transcripts of p53 were found in BTL-PC3 and BLT2 lines, but not in BLS1. Madin Darby bovine kidney cell line expressed multiple cellular oncogenes, c-jun, c-myc, and c-fos, and p53 genes. Southern blot hybridization did not reveal abnormal DNA rearrangements associated with the expressed oncogenes (c-myc and c-myb) in the 3 bovine tumor lines. (ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Specific expression of cellular oncogenes c-myc and c-myb in T-cell lines established from three types of bovine lymphosarcomas. 811 30

Activation of the human GADD45 gene by ionizing radiation (IR) has previously been shown to be dependent on the tumor suppressor and transcription factor p53 (M. B. Kastan, et al., Cell 71: 587-597, 1992). Unlike GADD45, the response of other DNA damage-inducible genes to IR is not dependent on p53 based on the observation that induction in a panel of cell lines did not correlate with a normal p53 status; this included human GADD153, another member of the gadd (growth arrest and DNA damage inducible) group; MyD118, a gene related to GADD45; and the protooncogenes c-jun and c-fos. This p53-dependent response of GADD45 was further investigated in human cells with halogenated pyrimidines, which act as radiosensitizers when incorporated into cellular DNA. When cellular DNA contained halogenated pyrimidines such as iododeoxyuridine (IdUrd), GADD45 gamma-ray induction, as measured by increased mRNA, was enhanced. Rapid induction could be seen with doses as low as 0.5 Gy, and substitution with IdUrd resulted in an approximately 2-fold increase in induction over a wide dose range. This level of IdUrd substitution produced a similar fold increase in cellular radiosensitivity and has been shown previously (T. M. Kinsella et al., Int. J. Radiation Oncology Biol. Phys. 13: 733-739, 1987) to produce a similar fold increase in DNA strand breaks after IR. Considering that substitution with halogenated pyrimidines would be expected to have little effect on other cellular targets after IR, these experiments indicate that actual damage to DNA, primarily strand breaks, is a major signal for the activation of this p53-dependent pathway that is required for GADD45 induction and for activation of the G1 "checkpoint" cell cycle delay.
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PMID:The p53-dependent gamma-ray response of GADD45. 816 7

By manipulating the circulating blood level of androgen, it is possible to induce either the programmed death (apoptosis) or proliferation of prostatic glandular cells. To examine the role of differential gene regulation in these two procedure, the expression of the mRNA of a series of genes was quantitated on a per cell basis during the androgen ablation-induced programmed death of rat prostatic glandular cells. These results were then compared to quantitative analysis of the mRNA expression of these same series of genes during the proliferative regrowth of prostatic glandular cells induced in rats castrated for 1 week before being treated with exogenous androgen replacement. These comparisons demonstrated that androgen ablation-induced programmed death of prostatic glandular cells share several (i.e. c-myc, H-ras, and tissue transglutaminase), but not most, of the epigenetic changes associated with androgen-stimulated proliferation of these cells. No enhancement of the mRNA expression of several genes required for entrance of prostatic glandular cells into the S-phase of the proliferative cycle (i.e. histone-H4, c-fos, p53, and ornithine decarboxylase) occurred during androgen ablation-induced programmed death of these cells. These results demonstrated that neither entrance into the S-phase nor progression through a defective proliferative cell cycle is involved in androgen ablation-induced programmed death of prostatic glandular cells. This was further supported by the observation that there is a set of genes (i.e. TRPM-2, transforming growth factor-beta 1, alpha-prothymosin, and calmodulin) in which mRNA expression is only enhanced during programmed cell death and not during proliferation of prostatic glandular cells induced by androgen replacement. These results demonstrate that prostatic programmed cell death is a distinct pathway from cell proliferation involving differential gene regulation.
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PMID:Differential gene regulation during programmed death (apoptosis) versus proliferation of prostatic glandular cells induced by androgen manipulation. 824 89

Differentiation of cells in the mouse myogenic cell line C2, or a primary culture of chicken satellite cells was induced by low serum levels in the growth medium. Endogenous wild-type p53 mRNA was substantially expressed after approximately 5 h of incubation. Induction of p53 mRNA expression was also observed in cells treated with 10(-8) M retinoic acid, after 18 h of incubation. In both cases, the increase in p53 mRNA was transient. c-fos mRNA levels decreased rapidly and were barely detectable after 2 h of exposure to retinoic acid. The down-regulation of c-fos confirms its role in muscle cell differentiation, whereas the up-regulation of wild-type p53 suggests its role during this process.
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PMID:p53 gene is up-regulated during skeletal muscle cell differentiation. 848 78


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