Resistance to p53-mediated growth suppression in human ovarian cancer cells retain endogenous wild-type p53.

Cancer cells containing mutated p53 are sensitive to the re-introduction of the wild-type (wt) p53. We sought to determine whether ovarian cancer cells that retain wt p53 are sensitive to the re-introduction of wt p53. Our results demonstrated that A2780 and PA-1 cells, which retain wt p53, are more resistant to apoptosis and growth suppression induced by exogenous expression of wt p53 than SKOV-3 and Caov-3 cells that contain mutated p53. All cell lines, except PA-1, showed induction of the p53-targeted genes. Further, inhibitors of p53-dependent apoptosis, mdm2 and Bcl-xL were not overexpressed in A2780 and PA-1 cells. These results suggest that one major defect in PA-1 cells is due to abrogation of induction of the p53-targets which is independent of mdm2 and Bcl-xL. Although A2780 cells showed induction of the p53-targeted genes, the cleavage of caspase-9 was undetectable. Therefore, p53-dependent apoptosis may be blocked upstream or at the caspase-9 level in A2780 cells.