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Query: UNIPROT:P04637 (p53)
 77,613 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have investigated the involvement of tumor suppressor genes in the genesis of osteosarcoma by analyzing allele losses at polymorphic loci in tumor tissues. Genotypes of DNA from primary osteosarcoma tissue and corresponding normal cells from 37 patients were analyzed at 58 polymorphic loci representing each autosomal chromosome arm except 5p and 20q. Allele losses were found at polymorphic loci on 36 of 37 chromosome arms analyzed. In particular, four of them showed frequencies of allele loss higher than 60%: 3q (75%); 13q (68%); 17p (72%); and 18q (64%). This result suggests that, in addition to the RB (retinoblastoma) gene on 13q and the p53 gene on 17p, at least two more tumor suppressor genes located on 3q and 18q are frequently involved in the development of osteosarcoma. The extent of allele losses as defined by fractional allelic loss among 36 tumors was diverse, from 0 to 0.64. The median fractional allelic loss value of 0.32 was much higher than those previously reported in colorectal carcinoma and breast carcinoma. Although no definite association of fractional allelic loss value to clinical prognosis of each case was found in osteosarcoma, tumors with 17p loss were more prone to the early onset of lung metastasis than tumors without 17p loss, indicating that allele loss on chromosome 17p can be a useful measure of prognosis.
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PMID:Allelotype analysis in osteosarcomas: frequent allele loss on 3q, 13q, 17p, and 18q. 156 11

The ability of the oncogene products of DNA tumor viruses to induce DNA synthesis in quiescent cells is thought to depend on their capacity to bind to cellular proteins such as the retinoblastoma-suppressor protein Rb and the tumor suppressor p53, thereby abolishing the growth-arresting properties of these proteins. We have tested this hypothesis using SV40 T antigens carrying lesions that affect Rb binding, p53 binding or other functions involved in cell transformation. The results demonstrate that Rb binding is not essential for growth stimulation by T antigen. However, detailed analysis, including intracistronic complementation, suggests that at least three functions, Rb binding, a novel second activity localized to the DNA-binding domain and a function residing in the carboxy terminus, probably p53 binding, cooperate to generate the full growth induction potential of T antigen.
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PMID:Intracistronic complementation reveals a new function of SV40 T antigen that co-operates with Rb and p53 binding to stimulate DNA synthesis in quiescent cells. 157 Jan 54

Clones of mortal chicken fibroblasts and erythroblasts transformed by temperature-sensitive v-src and v-erb B oncoproteins have been developed into immortal cell lines that retain the conditional transformed phenotype. The expressions of two tumor suppressor genes, the retinoblastoma (Rb) gene and the p53 gene, were investigated during senescence, crisis, and cell line establishment. In temperature-sensitive (ts)-v-erb B erythroblasts and ts-v-src fibroblasts (as well as in v-myc macrophages), loss of p53 mRNA or expression of a mutated p53 gene invariably occurred in the early phase of immortalization. In contrast, expression of the Rb gene was unchanged at all stages of immortalization. Inactivation of the original temperature-sensitive oncogene led to loss of the transformed phenotype in fibroblasts and to differentiation in erythroblasts, even in lines that were immortal and lacked p53. The results demonstrate that the process of immortalization is distinct from cell transformation, probably requiring different mutational events.
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PMID:Immortalization of conditionally transformed chicken cells: loss of normal p53 expression is an early step that is independent of cell transformation. 157 79

In the past year, two tumor suppressor genes, retinoblastoma and p53, have been established as important players in cell-cycle control, mediated by phosphorylation and by stage-specific transcription complexes. Evidence that they also participate in other transcription complexes is accumulating and searches are underway for the downstream genes under their regulation. Genes down-regulated in tumor cells are being screened by subtractive hybridization to bridge the gap between transcription factors and their targets.
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PMID:Tumor suppressor genes in the cell cycle. 159 86

Mutation of the p53 gene is one of the most frequent genetic changes found in human cancers. Recent experiments indicated that p53 might contain a transcription-activating domain, which functions when directed to a promoter. This study shows that wild-type p53 suppresses transcription of the retinoblastoma (Rb) gene. From deletion and mutagenesis experiments, a cis-acting element (GGAAGTGA) susceptible to regulation by p53 was mapped within the Rb promoter. This element overlaps the basal transcription unit of the Rb promoter, suggesting that p53 suppresses Rb transcription through inhibition of the basal promoter activity. The N-terminal acidic and C-terminal basic domains of p53 were both required for this suppression. These findings indicate that p53 can act as a transcriptional regulator in vivo.
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PMID:Negative regulation of Rb expression by the p53 gene product. 160 30

Genetic analyses of unusual hereditary cancers and of common neoplasms suggest that tumorigenesis proceeds through a series of genetic alterations involving oncogenes and tumor-suppressor genes. Such genes can be viewed as tumor-susceptibility genes, and DNA tests that examine them might be useful in determining an increased risk of cancer development before the onset of a tumor. Indeed, DNA tests have already proved useful in the genetic counseling of families with an increased risk of rare inherited diseases such as retinoblastoma, multiple endocrine neoplasia type 2a, or Li-Fraumeni syndrome. The current investigation of these familial disorders is enabling the development of expertise, reagents, and methods that will eventually focus on the most common cancers. In assessing risk for these common tumors, several genes will probably require study to achieve more accurate prediction of cancer risk. For example, genetic abnormalities of the ras oncogene and of either the retinoblastoma gene (Rb) or the p53 tumor-suppressor gene have been found in many tumors and appear to be particularly important in the study of individuals at increased risk of lung, breast, or colon cancers. In addition, the study of tumor-associated markers that might already be detectable in the preneoplastic state can be carried out in parallel with tests that search for evidence of mutations in tumor-susceptibility genes. Finally, both classes of markers might be complementary in genetic counseling or screening of populations at increased risk. However, the capacity for detecting tumor-susceptibility markers creates a responsibility for the physician in terms of the proper use of this information.
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PMID:Tumor-susceptibility markers. 161 94

Human cervical carcinoma cell lines that were either positive or negative for human papillomavirus (HPV) DNA sequences were analyzed for evidence of mutation of the p53 and retinoblastoma genes. Each of five HPV-positive cervical cancer cell lines expressed normal pRB and low levels of wild-type p53 proteins, which are presumed to be altered in function as a consequence of association with HPV E7 and E6 oncoproteins, respectively. In contrast, mutations were identified in the p53 and RB genes expressed in the C-33A and HT-3 cervical cancer cell lines, which lack HPV DNA sequences. Mutations in the p53 genes mapped to codon 273 and codon 245 in the C33-A and HT-3 cell lines, respectively, located in the highly conserved regions of p53, where mutations appear in a variety of human cancers. Mutations in RB occurred at splice junctions, resulting in in-frame deletions, affecting exons 13 and 20 in the HT-3 and C-33A cell lines, respectively. These mutations resulted in aberrant proteins that were not phosphorylated and were unable to complex with the adenovirus E1A oncoprotein. These results support the hypothesis that the inactivation of the normal functions of the tumor-suppressor proteins pRB and p53 are important steps in human cervical carcinogenesis, either by mutation or from complex formation with the HPV E6 and E7 oncoproteins.
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PMID:The state of the p53 and retinoblastoma genes in human cervical carcinoma cell lines. 164 18

We have examined a series of squamous cell carcinomas (SCC) of the anus, anal intraepithelial neoplasia grade III (AINII) lesions and haemorrhoids for the presence of sequences from transforming human papillomavirus (HPV) types by polymerase chain reaction (PCR)/Southern blotting. In addition, the same DNAs have been analysed for abnormalities in the c-myc, p53 and retinoblastoma (Rb-1) gene loci by Southern blotting. HPV16 sequences were detected in a total of 38 of 50 (76%) and HPV18 sequences in 4 of the 50 cancers (8%). Of 12 haemorrhoids examined, none contained HPV16 or HPV18 sequences. Amplification of c-myc was demonstrated in 15 of the 50 cancers (30%), of which 13 were HPV16 positive, and one also positive for HPV18. Amplification of c-myc was not observed in the 5 AINIII or any of the 41 haemorrhoid DNAs analysed. Rearrangement of c-myc was not seen in any of the DNAs. Gross rearrangement, or loss of p53 or Rb-1 loci was not observed in any normal or tumor tissue. However, in preliminary analysis of p53 sequence, three tumours negative for HPV were heterozygous for p53 point mutation whereas six HPV positive tumours and two haemorrhoids were wild-type sequence throughout exons four to ten.
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PMID:Status of c-myc, p53 and retinoblastoma genes in human papillomavirus positive and negative squamous cell carcinomas of the anus. 165 Apr 45

The aberrant overexpression of interleukin 6 (IL-6) is implicated as an autocrine mechanism in the enhanced proliferation of the neoplastic cell elements in various B- and T-cell malignancies and in some carcinomas and sarcomas; many of these neoplasms have been shown to be associated with a mutated p53 gene. The possibility that wild-type (wt) p53, a nuclear tumor-suppressor protein, but not its transforming mutants might serve to repress IL-6 gene expression was investigated in HeLa cells. We transiently cotransfected these cells with constitutive cytomegalovirus (CMV) enhancer/promoter expression plasmids overproducing wt or mutant human or murine p53 and with appropriate chloramphenicol acetyltransferase (CAT) reporter plasmids containing the promoter elements of human IL-6, c-fos, or beta-actin genes or of porcine major histocompatibility complex (MHC) class I gene in pN-38 to evaluate the effect of the various p53 species on these promoters. Murine and human wt p53 derived from pCMVNc9 and pC53-SN3, respectively, strongly repressed the IL-6 (promoter position -225 to +13), c-fos (-711 to +42), beta-actin (-3400 to +912), and MHC (-528 to -38) promoters in serum-induced HeLa cells; additionally, IL-6 promoter/CAT transcription unit constructs induced by IL-1, phorbol ester, or pseudorabies virus were also repressed by wt human and murine p53. The murine transforming mutant p53 (pCMVc5) was less active in repressing the IL-6, c-fos, beta-actin, and MHC promoter constructs. The human p53 mutant derived from pC53-SCX3 was also less active than the wt protein in repressing the IL-6, c-fos, beta-actin, and MHC promoters, except that serum-induced IL-6/CAT expression was equally repressed by both human wt and mutant p53. In similar transient transfection experiments in HeLa cells, overexpression of the wt human retinoblastoma susceptibility gene product, RB, was found to repress the serum-induced IL-6 (-225 to +13), c-fos (-711 to +42), and beta-actin (-3400 to +912) promoters but not the PRV-induced IL-6 (-110 to +13) or the serum-induced MHC (-528 to -38) promoters. These observations identify transcriptional repression as a property of p53 and suggest that p53 and RB may be involved as transcriptional repressors in modulating IL-6 gene expression during cellular differentiation and oncogenesis.
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PMID:Repression of the interleukin 6 gene promoter by p53 and the retinoblastoma susceptibility gene product. 165 55

Aberrations of the p53 gene in 43 primary hepatocellular carcinomas (HCCs) were examined by single-strand conformation polymorphism analysis of polymerase chain reaction products. Of these hepatocellular carcinomas, 22 were advanced HCCs, and 21 were early HCCs. Structural abnormalities of the p53 gene were observed in eight of the 22 advanced HCCs, but in none of the early HCCs. Of the eight tumors with an abnormal p53 gene, seven had lost one of the two p53 alleles and, in the seven tumors with identifiable mutations, point mutations were found in four tumors and deletions of several nucleotides were observed in two tumors. The remaining one retained both alleles and carried two point mutations. In addition to the aberrations of the p53 gene, loss of the retinoblastoma gene or loss of heterozygosity at chromosome 13q was observed in six of seven informative cases of eight tumors carrying a mutated p53 gene. These results suggest the involvement of at least two tumor suppressor genes in a late stage of hepatocarcinogenesis.
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PMID:Aberrations of the tumor suppressor p53 and retinoblastoma genes in human hepatocellular carcinomas. 165 54


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