Low levels of expression of an inhibitor of cyclin-dependent kinases (CIP1/WAF1) in primary breast carcinomas with p53 mutations.
Recently, several groups have isolated a cell cycle inhibitor gene (CIP1/WAF1) that is highly induced by wild-type, but not mutant forms of the p53 tumor suppressor. To test the hypothesis that p53 regulates CIP1/WAF1 expression in vivo, we evaluated CIP1/WAF1 mRNA expression levels in breast carcinomas from individuals with axillary node-negative disease with and without p53 mutations using quantitative reverse transcription-PCR. The data demonstrate that there is a strong negative correlation between the presence of p53 mutations and CIP1/WAF1 expression, suggesting that p53 mutations may reduce its ability to induce CIP1/WAF1 in vivo. In this study we observed tumors with low levels of CIP1/WAF1 mRNA in which there were no detectable p53 mutations. Determination of the CIP1/WAF1 levels in such specimens may provide a complementary strategy for analyzing the effects of p53 defects and/or may suggest the presence of alterations (such as coding mutations outside the conserved regions, promoter mutations, etc.) that may be missed by standard techniques.
Ozçelik
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Samuel Lunenfeld Research Institute, Mount Sinai Hospital, and Departments of Cellular and Molecular Pathology, Toronto, Ontario M5G 1X5, Canada.
Mousses
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Andrulis
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D019943:Amino Acid Substitution; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D002453:Cell Cycle / Q000235:genetics; D018388:Codon, Terminator; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000032:analysis / Q000235:genetics*; D004791:Enzyme Inhibitors / Q000032:analysis; D005260:Female; D016368:Frameshift Mutation; D015972:Gene Expression Regulation, Neoplastic; D016158:Genes, p53; D018922:HL-60 Cells; D006801:Humans; D009154:Mutation; D017354:Point Mutation; D018807:Polymorphism, Single-Stranded Conformational; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured
C493956:CDKN1A protein, human; D018388:Codon, Terminator; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D004791:Enzyme Inhibitors; D012333:RNA, Messenger