EXPRESSION OF P21(WAF1/CIP1) IS HETEROGENEOUS AND UNRELATED TO PROLIFERATION INDEX IN HUMAN OVARIAN-CARCINOMA

The growth-inhibitory protein p21(WAF1/CIP1) is, a potent inhibitor of various cyclin dependent kinases, the expression of which is regulated at the transcriptional level by p53-dependent and -independent mechanisms. We examined p21(WAF1/CIP1) mRNA and protein expression in 5 human ovarian-adenocarcinoma cell lines, primary culture of normal surface epithelium and 17 human ovarian-tumor specimens. In culture cells, the p21(WAF1/CIP1) protein was expressed in normal ovarian epithelial cells and at a high level in the adenocarcinoma 2008 and IGROV-1 cell lines. p21(WAF1/CIP1) expression was undetectable at the mRNA and protein levels in the NIH-OVCAR-3 and SKOV-3 ovarian-adenocarcinoma cell lines which are respectively mutated and deleted in the p53 gene. Heterogeneous expression of p21(WAF1/CIP1) observed in ovarian-cancer cell lines in culture was also found in vivo on tumor specimens. p21(WAF1/CIP1) expression is undetectable in 25% of the ovarian biopsies examined. Since it has been found that the p53 gene is mutated in 79% of ovarian cancer, the absence of p21(WAF1/CIP1) expression in 25% of these ovarian cancer could not be correlated with p53 mutation. The proliferation index of the 17 tumors showed great variation from one tumor to another. However, no significant correlation was found between p21(WAF1/CIP1) expression and the proliferation rate of the tumors. (C) 1995 Wiley-Liss, Inc.