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)

Inactivating mutations of the retinoblastoma gene (RB) are found in a wide variety of tumour cells. Replacement of wild-type RB can suppress the tumorigenicity of some of these cells, suggesting that the RB protein (Rb) may negatively regulate cell growth. As activation of c-myc expression promotes cell proliferation and blocks differentiation, it may positively regulate cell growth. The c-myc protein is localized in the nucleus and can physically associate with RB protein in vitro, hence c-myc may functionally antagonize RB function. Microinjection of Rb in G1 phase reversibly arrests cell-cycle progression. Here we co-inject RB protein with c-myc, EJ-ras, c-fos or c-jun protein. Co-injection of c-myc, but not EJ-ras, c-fos or c-jun, inhibits the ability of Rb to arrest the cell cycle. The c-myc does not inhibit the activity of another tumour supressor, p53 (ref. 12). Thus, c-myc and RB specifically antagonize one another in the cell.
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PMID:Abrogation by c-myc of G1 phase arrest induced by RB protein but not by p53. 143 95

The induction of murine erythroleukemia cells (MELC) to terminal differentiation by hexamethylene bisacetamide (HMBA) is accompanied by changes in the levels of c-myb and c-myc mRNA, and in p53 protein levels. We simultaneously examined the effects of HMBA on modulation of c-myb, c-myc and p53 mRNA and protein levels, and examined the relationship between these changes and commitment to terminal cell division. In MELC cultured with HMBA, c-myb protein levels paralleled c-myb mRNA levels except at 24h, when the protein level was equivalent to the level in control cultures, whereas the mRNA had decreased. The c-myc protein paralleled c-myc mRNA throughout induction. The p53 mRNA and protein behaved in a discordant fashion. The p53 protein decreased to very low levels between 4 and 8 h and remained low, while the mRNA, which initially decreased, reaccumulated by 24 and 48 h. Transfer of MELC after 12 to 48 h of culture with HMBA to medium without inducer resulted in rapid (less than 3 h) reaccumulation of the c-myb mRNA, c-myb protein, and p53 protein, and cessation of recruitment of cells to commitment. Cells already induced to commit to terminal differentiation continued to express the differentiated phenotype.
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PMID:Modulation of the c-myb, c-myc and p53 mRNA and protein levels during induced murine erythroleukemia cell differentiation. 264 54

We have shown that geldanamycin (GDM), an antibiotic of benzoquinoid ansamycin group, inhibits DNA replication in cultured mouse lymphoblastoma L5178Y cells. Here we report that GDM selectively inhibited the expression of c-myc gene, proto-oncogene, along with suppression of DNA replication in L5178Y cells, which are consistent with our previous results that c-myc protein promotes cellular DNA replication. The significantly enhanced inhibition by GDM of DNA replication was observed, when the antibiotic was introduced at G1 stage prior to S phase of cell cycle. The results are in favor of the prospects that GDM inhibits DNA replication mainly at time of initiation, and that c-myc protein is essential for the initiation of cellular DNA replication. Furthermore, when c-myc expression was inhibited by GDM, the expression of p53 gene, the product of which may be another DNA replication protein, was stimulated in the tumor cells. Thus, GDM should be useful to investigate the molecular mechanism of DNA replication promoted by c-myc protein and also to distinguish the function of c-myc protein from that of p53 protein in DNA replication.
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PMID:Inhibition of c-myc gene expression in murine lymphoblastoma cells by geldanamycin and herbimycin, antibiotics of benzoquinoid ansamycin group. 265 16

Amplification of the c-myc gene has been frequently reported in breast carcinomas. However the precise function of the c-myc protein is still unknown and the nature of the selective advantage offered to a cell by an overexpression of such a protein is unclear. We are addressing this question using the SW 613-S human breast carcinoma cell line as a model system. This cell line harbours an amplified c-myc gene and a mutated c-Ki-ras gene. By various criteria the amplified c-myc gene of SW613-S cells appears undistinguishable from a normal human c-myc gene. The SW613-S cell line is heterogeneous: it contains cells with a high level of amplification and carrying the extra copies of the c-myc gene in double minute chromosomes (DMs) and cells with few c-myc genes integrated into chromosomes. DM-containing cells are progressively lost upon in vitro cultivation but are selected for during in vivo growth, as tumors in nude mice, or by cultivating the cells in a chemically defined, serum-free medium or under conditions preventing anchorage. Clones with different levels of amplification and different chromosomal localization of the c-myc copies were isolated from the SW 613-S cell population. Those with a high level of amplification and expression of the c-myc gene are tumorigenic in nude mice, whereas those with a low level are not. Introduction of c-myc gene copies by transfection confers tumorigenicity to the nontumorigenic clones, indicating that a high level of amplification of the c-myc gene contributes to the tumorigenic phenotype of SW 613-S cells. Tumorigenic clones grow unattached, are able to proliferate in a chemically defined medium, and produce high levels of several growth factors (e.g. TGF-alpha, IGF2). Nontumorigenic clones are more dependent upon anchorage for growth, show a restricted growth in defined medium, and produce low or undetectable level of the growth factors tested. We have identified several genes, besides c-myc, the expression level of which is markedly different in the two types of clones. TGF-alpha, IGF2, PDGF-A, int-2, cytokeratins K8 and K18 and ferritin H chain are overexpressed in tumorigenic clones. In contrast, c-erbB1 (EGF receptor), c-jun, vimentin and p53 are expressed at a higher level in the nontumorigenic clones. Finally the major histocompatibility class I antigens, ferritin L chain, TGF-beta and c-Ki-ras, are examples of genes expressed at the same level in both types of clones.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:The human breast carcinoma cell line SW 613-S: an experimental system to study tumor heterogeneity in relation to c-myc amplification, growth factor production and other markers (review). 268 29

We have recently reported that the c-myc protein may promote cellular DNA replication by binding to the origin of DNA replication (ori) and that an origin of human DNA replication which can autonomously replicate in human cells was cloned as a binding sequence of c-myc protein (Iguchi-Ariga et al., 1987). Here we report that cellular tumor antigen p53 may also participate in cellular DNA replication and another origin of DNA replication was cloned as a possible p53-binding sequence. The sequence could autonomously replicate in Raji cells which express p53 at a high level but not in HL-60 cells in which the coding gene for p53 is largely deleted. Little homology of the sequences was found between c-myc protein-binding ori and p53-binding ori. This suggests that c-myc protein and p53 may independently recognize different ori in chromosomal DNA.
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PMID:Cloning of the p53-dependent origin of cellular DNA replication. 297 68

We have examined the effect that microinjection of a monoclonal antibody directed against human DNA polymerase-alpha (SJK-287) has on DNA synthesis in exponentially growing human, mouse, and hamster cell lines. We show that the SJK-287 antibody, when microinjected directly into the nuclei of cells is capable of inhibiting DNA synthesis in all three cell lines tested. Moreover, the effectiveness with which this antibody can inhibit ongoing DNA synthesis by the microinjection assay is closely correlated with the ability of the antibody to neutralize DNA polymerase-alpha activity fractionated from each cell line in vitro. Two other monoclonal antibodies of the same class, one directed against the cellular p53 protein (PAb122), and one directed against the c-myc protein (PM-8) were also tested for their ability to inhibit ongoing DNA synthesis by direct microinjection and in lysolecithin permeabilized cells. Both monoclonal antibodies failed to inhibit ongoing DNA synthesis in exponentially growing cells by these assays.
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PMID:A microinjected monoclonal antibody against human DNA polymerase-alpha inhibits DNA replication in human, hamster, and mouse cell lines. 373 34

We investigated apoptosis by nick end labeling and the expression of apoptosis-related proteins by immunohistochemistry in fetal development of human intrahepatic bile ducts and hepatocytes. During intrahepatic bile duct development, apoptosis was present at all stages, and its positive ratio was high in the remodeling ductal plate, moderate in the ductal plate, and relatively low in remodeled ducts. The cell proliferative activity as determined by proliferating cell nuclear antigen was also high in the remodeling ductal plate, and relatively low in the ductal plate and remodeled ducts. fas antigen and c-myc protein were constantly positive in the ductal plate, remodeling ductal plate and remodeled ducts. Bcl-2 protein was negative or faintly positive in the ductal plate and remodeling ductal plate, but was apparently positive in remodeled ducts. Lewisy as detected by the BM-1 antibody was present in the ductal plate, remodeling ductal plate, and remodeled ducts. p53 protein was not found in any cell types in the liver development. During hepatocyte development, many apoptotic and proliferating cell nuclear antigen-positive hepatocytes were noted. The developing hepatocytes expressed c-myc protein and fas antigen. Bcl-2 protein and Lewisy antigen were also weakly positive in the developing hepatocytes. These findings showed that balanced cell proliferation and apoptosis are involved in the normal development of intrahepatic bile ducts and hepatocytes, and suggest that c-myc protein, fas antigen, Bcl-2 protein, and Lewisy antigen modulate apoptosis of fetal intrahepatic biliary cells and hepatocytes, probably by stimulative (c-myc protein and fas and Lewisy antigens) or inhibitory (Bcl-2 protein) effects.
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PMID:Detection of apoptosis and expression of apoptosis-related proteins during human intrahepatic bile duct development. 753 50

Archival biopsy specimens from transitional cell bladder tumours (n = 185) were analysed immunohistochemically for expression of c-myc protein. The results were compared with histopathological and clinical parameters and survival. Forty-three per cent of the tumours were negative for c-myc protein and weak, moderate, or strong cytoplasmic expression was found in 34, 14, and 9 per cent of cases, respectively. Nuclear positivity for c-myc protein was detected in 35 per cent of tumours and nuclear positivity was related to overexpression of c-erb B-2 (P = 0.01) and a high proportion of nuclei were also positive for p53 oncoprotein (p < 0.05). Cytoplasmic expression of c-myc protein was related to histological grade (P = 0.005), papillary status (P = 0.007), the S-phase fraction (P = 0.008), the mitotic index (P = 0.021), overexpression of epidermal growth factor receptor (P = 0.045), and c-erb B-2 (P = 0.17). Expression of c-myc protein was not significantly related to the progression of tumours and it had no prognostic value in survival analysis. Independent predictors were the T-category (P < 0.001), papillary status. (P = 0.001), and S-phase fraction (P = 0.061). The results show that while c-myc gene product participates in growth regulation of human bladder cancer cells, it has no independent prognostic significance.
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PMID:Expression of c-myc protein is related to cell proliferation and expression of growth factor receptors in transitional cell bladder cancer. 773 16

Amplification and overexpression of c-myc have been suggested as prognostic markers in human cancer. To assess the role of c-myc gene copy number alterations in bladder cancer, 87 bladder tumors were examined for c-myc aberrations by fluorescence in situ hybridization. Dual labeling hybridization with a repetitive pericentromeric probe specific for chromosome 8 and a probe for the c-myc locus (at 8q24) was performed to analyze c-myc copy number in relation to chromosome 8 copy number on a cell by cell basis. A clear-cut c-myc amplification (up to 40 to 150 copies per cell) was found in 3 tumors. There was a low level c-myc copy number increase in 32 of the remaining 84 tumors. There was no association of low level c-myc copy number increase with c-myc protein overexpression. This suggests that a c-myc gene copy number gain as detected by fluorescence in situ hybridization does not necessarily reflect a disturbed c-myc gene function but may indicate a structural chromosome 8 abnormality including gain of distal 8q. The strong association of low level c-myc (8q) gains with tumor grade (P < 0.0001), stage (P < 0.0001), chromosome polysomy (P < 0.0001), p53 protein expression (P = 0.0019), p53 deletion (P = 0.0403), and tumor cell proliferation (Ki67 labeling index; P = 0.0021) is consistent with a role of chromosome 8 alterations in bladder cancer progression.
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PMID:c-myc copy number gains in bladder cancer detected by fluorescence in situ hybridization. 774 7

Bovine papillomavirus type 1 (BPV-1)-transformed mouse fibroblast cell lines were analyzed via flow cytometry (FCM) for expression of p53 and c-myc proteins along with their DNA content. In comparison to the nontransformed control cell line, significantly elevated levels of both the p53 and the c-myc protein were present in some but not all of the transformed cell lines. Quantitation of p53 and c-myc proteins in cell lines containing BPV-1 DNA revealed that the tumorigenic cell lines expressed higher levels of both the p53 (P = 0.0034; Mann-Whitney U test) and the c-myc protein (P = 0.0039; Mann-Whitney U test) as compared to the nontumorigenic cell lines. On average, at least 9,000-10,000 p53 or c-myc protein molecules per cell were detected in the transformed tumorigenic cell lines. These results show that quantitative FCM can be reliably used to detect very low levels (3,000 molecules per cell) of specific protein, and FCM is a useful tool to study the virus-induced changes in the levels of nuclear proteins within a cell population and in tumorigenesis.
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PMID:Flow cytometric quantitation of C-myc and P53 proteins in bovine papillomavirus type 1-transformed primary mouse fibroblasts. 785 Nov 59


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