Low levels of expression of an inhibitor of cyclin-dependent kinases (CIP1/WAF1) in primary breast carcinomas with p53 mutations.

Abstract

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.