Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P04637 (p53)
 77,613 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
 ...
PMID:Highly efficient focus formation by Rous sarcoma virus on adenovirus type 12 E1A-transformed rat 3Y1 cells. 131 Jul 57

Monolayer cultures of human foreskin and ectocervical epithelial cells were infected with retroviral vectors expressing HPV16 oncogenes, selected for G418 resistance, and cultured organotypically so that they reformed the fully differentiated, stratified squamous tissues from which they were originally derived. Expression of HPV16 E7 prevented cell cycle withdrawal in the suprabasal layers of these stratified cultures but had no effect on terminal differentiation. Cultures expressing E7 alone and those coexpressing E6 and E7 were identical in terms of suprabasal proliferation and terminal differentiation, but they differed in expression of the endogenous tumor suppressor protein p53. Immunohistochemically detectable p53 protein localized to the proliferative compartment in normal and E7-containing cultures but was undetectable in those cultures which coexpressed E6 and E7. This result suggests that E7-induced suprabasal proliferation is independent of the steady-state level of p53.
 ...
PMID:Expression of the HPV16 E7 gene generates proliferation in stratified squamous cell cultures which is independent of endogenous p53 levels. 133 93

Several studies have shown that expression of exogenous wild-type p53 is detrimental to the growth of cell lines with absent or mutant p53. In this study, wild-type p53 cDNA expression plasmids were transfected into A549 lung carcinoma cells which had previously been shown by sequencing to contain wild-type p53. When a constitutively expressed wild-type p53 plasmid containing the neomycin resistance gene was transfected into these cells, no G418-resistant colonies contained the exogenous p53 cDNA even though the neomycin resistance gene was integrated. When cells were transfected with a dexamethasone-inducible wild-type p53 cDNA expression plasmid, induction of p53 expression resulted in a decreased growth rate and a decreased proportion of S-phase cells. Continuous treatment with dexamethasone resulted in continued p53 expression for 16 days, but beyond that time expression ceased and could not be reinduced. These data indicated that although the A549 cell line could proliferate in the presence of endogenous wild-type p53 there was a strong selection pressure against continued expression of additional exogenous wild-type p53.
 ...
PMID:Effects of exogenous wild-type p53 on a human lung carcinoma cell line with endogenous wild-type p53. 145 95

To identify regions on the large T antigens of simian virus 40 (SV40) and polyomavirus which are involved in oncogenic transformation, we constructed plasmids encoding hybrid polyomavirus-SV40 large T antigens. The hybrid T antigens were expressed in G418 sulfate-resistant pools of rat F2408 cells, and extracts of such pools were immunoprecipitated with an antibody against p53. Two hybrid T antigens containing SV40 amino acids 337 to 708 bound to p53, whereas another hybrid T antigen containing SV40 amino acids 412 to 708 did not. This suggests that a binding domain on SV40 large T antigen for p53 is contained within amino acids 337 to 708, with amino acids 337 to 411 playing an important role. One of the two hybrids that bound to p53 was chosen for further study. This T antigen contained SV40 large T antigen amino acids 336 to 708 joined to polyomavirus large T antigen amino acids 1 to 521 (PyT1-521-SVT336-708). Immunoprecipitation with antibodies directed against the product of the retinoblastoma susceptibility gene, p105-RB, showed that this hybrid bound p105-RB as well as p53. Pools expressing the hybrid PyT1-521-SVT336-708 did not grow in soft agar, nor did they form foci on confluent monolayers of nontransformed F2408 cells. The hybrid T antigen was expressed at levels comparable to those seen in retrovirus-infected F2408 cells expressing only SV40 large T antigen, which do show a transformed phenotype. Thus, this level of expression was sufficient for transformation by SV40 large T antigen but not for the hybrid large T antigen. These data, combined with genetic studies from other laboratories, suggest that complex formation with p53 and p105-RB is necessary but not sufficient for the oncogenic potential of papovavirus large T antigens.
 ...
PMID:Binding of p53 and p105-RB is not sufficient for oncogenic transformation by a hybrid polyomavirus-simian virus 40 large T antigen. 221 17

p53 anti-sense sequences were introduced into normal NIH3T3 and transformed CMS 4 cells by infection with the recombinant retrovirus carrying a repeat of the 5'-terminal fragment of p53 cDNA. Clones selected for G418 resistance showed a marked inhibition of proliferative capacity and a reduced ability to enter DNA replication after stimulation of quiescent cells with serum. Clones showing moderate inhibition of proliferation were shown to contain truncated anti-sense DNA integrated into the genome. The anti-sense DNA was transcribed and it correlated with the reduction of the p53 protein level in the cell clones studied. We conclude that the appropriate expression of p53 appears to be required for cell proliferation.
 ...
PMID:[Antisense RNA p53 inhibits proliferation of normal and transformed cells]. 246 39

Some, but not all, mouse p53 genes are able to cooperate with an activated ras oncogene to transform primary cells. Overexpression of what is presumed to be wild-type murine p53 is sufficient to confer a tumorigenic phenotype on established cell lines. We have investigated the effect of overexpression of normal human p53 genes on the growth and morphology of both primary and established mouse and rat cells. When plasmids containing functional human p53 genes under the control of strong viral promoter/enhancer elements were transfected into NIH3T3 cells or Rat-1 cells, no gross alterations in cell shape or morphology were observed. When stable NIH3T3 transfectants were established by co-transfection of the p53 plasmids with pSV2neo and subsequent selection in medium containing G418, many of the lines generated exhibited altered growth characteristics. While, again, the cells did not form foci above the monolayer and were not capable of growing in soft agar, they showed a reduced dependence on serum for growth, were able to grow to higher saturation densities, and displayed markedly enhanced tumorigenicity when inoculated into nude mice. The expression of human p53 in the transfectants was assessed by immunoblotting with a monoclonal antibody, PAb1801, which is reactive to human but not mouse p53. There was a clear correlation between the extent of p53 overexpression and acquisition of the tumorigenic phenotype. None of nine human p53 constructs was capable of cooperating with an activated ras oncogene to transform primary cells under conditions where a mouse clone, pLTRp53cG, could do so efficiently. None of the human p53 constructs was capable of rescuing primary rat cells from senescence. Taken together, these data show that overproduction of normal human p53 can confer an enhanced tumorigenic phenotype on established fibroblasts and support the idea that mutational activation may be necessary for p53 to express its full oncogenic potential.
 ...
PMID:Overexpression of normal human p53 in established fibroblasts leads to their tumorigenic conversion. 265 16

We have tested the ability of chrysotile asbestos fibers to introduce plasmid DNA into monkey COS-7 cells and the ability of this DNA to function in both replication and gene expression. Chrysotile fibers are at least as effective as calcium phosphate in standard transfection assays at optimal ratios of asbestos to DNA. After transfection with chrysotile, a minor percentage of introduced plasmid DNA bearing a simian virus 40 origin of replication replicates after 24 hr. Fragmentation of entering DNA is more prominent with asbestos than with calcium phosphate, and after 72 hr most DNA introduced by asbestos is associated with chromosomal DNA. Cells transfected with plasmid p11-4, bearing the p53 protooncogene, express this gene. Cells transfected with pSV2-neo express a gene conferring resistance of antibiotic G418, allowing isolation of colonies of transformed cells after 18 days. The introduction of exogenous DNA into eukaryotic cells could cause mutations in several ways and thus contribute to asbestos-induced oncogenesis.
 ...
PMID:Asbestos fibers mediate transformation of monkey cells by exogenous plasmid DNA. 284 18

Recombinant retroviruses that transduce the simian virus 40 (SV40) large T antigen or the polyomavirus large T antigen as well as encoding resistance to antibiotic G418 were used to investigate whether these genes alone were sufficient for immortalization of primary cells. The results provided definitive evidence that either viral gene can efficiently establish primary fibroblasts. The capability of the SV40 large T antigen to establish primary fibroblasts was undiminished by a mutation that alters its binding to sequences within the origin of replication. Surprisingly, most of the primary cells established by the expression of the SV40 large T antigen did not have a transformed phenotype. This suggests that transformation by SV40 is not simply due to a high level of expression of the SV40 large T antigen and stabilization of cellular p53.
 ...
PMID:Large T antigens of simian virus 40 and polyomavirus efficiently establish primary fibroblasts. 301 37

We used a murine retrovirus shuttle vector system to construct recombinants capable of constitutively expressing the simian virus 40 (SV40) large T antigen and the polyomavirus large and middle T antigens as well as resistance to G418. Subsequently, these recombinants were used to generate cell lines that produced defective helper-free retroviruses carrying each of the viral oncogenes. These recombinant retroviruses were used to analyze the role of the viral genes in transformation of rat F111 cells. Expression of the polyomavirus middle T antigen alone resulted in cell lines that were highly tumorigenic, whereas expression of the polyomavirus large T resulted in cell lines that were highly tumorigenic, whereas expression of the polyomavirus large T resulted in cell lines that were unaltered by the criteria of morphology, anchorage-independent growth, and tumorigenicity. More surprisingly, SV40 large T-expressing cell lines were not tumorigenic despite the fact that they contained elevated levels of cellular p53 and had a high plating efficiency in soft agar. These results suggest that the SV40 large T antigen is not an acute transforming gene like the polyomavirus middle T antigen but is similar to the establishment genes such as myc and adenovirus EIa.
 ...
PMID:Recombinant retroviruses encoding simian virus 40 large T antigen and polyomavirus large and middle T antigens. 302 76

To investigate the biological function of p53 in colon carcinoma cells, a wild-type p53 expression plasmid under the control of the human cytomegalovirus promoter was stably transfected into the human colon adenocarcinoma cell line WiDr, which carries a mutation of the p53 gene at codon 273. Exogenous wild-type p53 transcripts were detected at various expression levels in 8 of 117 G418-resistant clones. The growth rates of the wild-type p53+ clones in culture did not change significantly. The efficiency of colony formation in soft agar, however, was completely suppressed in two wild-type p53+ clones. This is the first to demonstrate the feasibility of stable transfection of the wild-type p53 gene under the control of non-inducible promoter in human colon cancer cells. The major alteration found was that wild-type p53+ cells which were incubated with anti-Fas IgM showed marked cytolysis with preferential over-expression of wild-type p53 accompanied by overexpression of a cyclin-dependent kinase inhibitor, WAF1, whereas the endogenous mutant p53 retained its expression level. The findings suggest that a Fas-initiated pathway is incidentally linked to a p53-dependent apoptotic pathway through the reconstituted wild-type p53 gene in WiDr cells. This model should help elucidating the additional role of the p53 tumor suppressor gene and the mechanism of apoptosis in colon carcinoma cells.
 ...
PMID:Induction of Fas-mediated apoptosis in p53-transfected human colon carcinoma cells. 747 11


1 2 3 4 5 6 7 Next >>