Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:B6E4X6 (mutant p53)
 3,342 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have screened the p53 status of 156 human cell lines, including 142 tumor cell lines from 27 different tumor types and 14 cell lines from normal tissues by using functional analysis of separated alleles in yeast. This assay enables us to score wild-type p53 expression on the basis of the ability of expressed p53 to transactivate the reporter gene HIS3 via the p53-responsive GAL1 promotor in Saccharomyces cerevisiae. Of 142 tumor cell lines, at least 104 lines (73.2%) were found to express the mutated p53 gene: 94 lines (66.2%) were mutated in both alleles, three lines (2.1%) were heterozygous, and no p53 cDNA was amplified from seven lines (4.9%). Of the 14 cell lines originating from normal tissues, all the transformed or immortalized cell lines expressed mutant p53 only. Yeast cells expressing mutant p53 derived from 94 cell lines were analyzed for temperature-sensitive growth. p53 cDNA from eight cell lines showed p53-dependent temperature-sensitive growth, growing at 30 degrees C but not at 37 degrees C. Four temperature-sensitive p53 mutations were isolated: CAT-->CGT at codon 214 (H214R), TAC-->TGC at codon 234 (Y234C), GTG-->ATG at codon 272 (V272M), and GAG-->AAG (E285K). Functionally wild-type p53 was detected in 38 tumor cell lines (26.8%) and all of the diploid fibroblasts at early and late population doubling levels. These results strongly support the previous findings that p53 inactivation is one of the most frequent genetic events that occurs during carcinogenesis and immortalization.
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PMID:Screening the p53 status of human cell lines using a yeast functional assay. 929 Jul 1

The accumulation of mutant p53 protein in cancer cells was observed by immunohistochemistry analysis. DNA was extracted from paraffin-embedded tissue. Exons 5, 7 and 8 were amplified and studied by PCR-SSCP and sequencing analysis. Ten cases of asbestos associated cancer tissue were studied, of which five cases had adenocarcinoma, and the other five had mesothelioma, squamous carcinoma, small cell lung cancer, adenosquamous carcinoma and malignant lymphoma respectively. Employing monoclonal antibody PAb1801, five cases were found to be mutant p53 protein positive. Seven cases were found to have mutations by PCR-SSCP. A total of 7 cases (8 mutations) were found to be positive and 4 cases were found to be positive by both of these analyses. Of the 8 mutations found by SSCP analysis, 4(50%, 4/8) were clustered in exon 8. A high mutation frequency was noticed in adenocarcinoma (80%, 4/5). Sequencing analysis on two specimens revealed two hotspot mutations. In codon 234, TAC for tyrosin was mutated to AAC for asparagine by a T to A transversion of the first letter. In codon 273, CGT for arginine was mutated to AGT for serine by a C to A transversion of the first letter. In conclusion, the mutation of p53 gene is common in asbestos associated cancers. However, the mutational spectrum of asbestos associated cancers might be different from that of non-asbestos associated cancers.
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PMID:p53 gene mutations in asbestos associated cancers. 986 81

Allele-specific competitive blocker PCR (ACB-PCR) amplification and quantification was developed for mouse p53 codon 270 CGT-->TGT base substitution and codon 244/245 AAC/CGC-->AAT/TGC tandem mutation. PCR products corresponding to p53 mutant and wild-type DNA sequences were generated. These DNAs were mixed in known proportions to construct samples with defined mutant fractions and the allele-specific detection of each mutation was systematically optimized. Each assay was used to analyze eight simulated solar light (SSL)-induced tumors. By analyzing mutant fraction (MF) standards in parallel with PCR products generated from tumor samples, p53 mutants could be quantified as subpopulations within the tumors. All eight tumors contained detectable levels of p53 codon 270 CGT-->TGT mutation. Three tumors had p53 MFs between 10(-4) and 10(-3). Five tumors had p53 MFs between 10(-3) and 10(-2). None of the eight mouse skin tumors had measurable levels of p53 codon 244/245 tandem mutation. Frequent detection of p53 codon 270 CGT-->TGT mutation provides additional evidence that a pyrimidine dinucleotide overlapping a methylated CpG site (Pyr(me)CG) is a susceptible target for SSL-induced mutagenesis. The absence of p53 codon 244/245 mutation in tumors may be explained by its mutant p53 phenotype and/or indicate that this site is not methylated. These initial results indicate that p53 codon 270 CGT-->TGT mutation may be a sensitive biomarker for SSL- or UV-induced mutagenesis. This mutational endpoint may be useful for evaluating the co-carcinogenicity of compounds administered in combination with UV or SSL.
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PMID:Quantifying levels of p53 mutation in mouse skin tumors. 1566 16