Ovarian cancer cells that coexpress endogenous Rb and p16 are insensitive to overexpression of functional p16 protein

Defects of the 'Rb/cyclin D1/p16 pathway' have been shown to play a critica l role in the development of virtually all human malignancies assessed. To determine the contribution of G1 phase cell cycle defects to ovarian tumori genesis, we have examined a panel of normal and tumor ovarian tissues and o varian cancer cell lines for the expression of Rb, p16 and cyclin D1 protei ns. Unlike most types of human cancer whose development involves the loss o f either Rb or p16 expression, we observed the coexpression of Rb, p16 and cyclin D1 in 82% of ovarian cancer tissues and cell lines, Furthermore, the growth and cell cycle distribution profiles of three ovarian cancer cell l ines (ES-2, PA-1 and NIH OVCAR-3) that coexpressed Rb and p16, were found t o be unaffected by adenoviral-mediated overexpression of functional p16 pro tein, indicating the existence of a defect(s) downstream from p16 in these cells. By contrast overexpression of ectopic p16 in the one ovarian cancer cell line (SK-OV3) that expressed Rb but lacked p16 protein, resulted in a G1 growth arrest. These data suggest that defects of the 'Rb/cyclin D1/p16 pathway', other than the loss of Rb or p16, may play a major role in the de velopment of ovarian cancer.