ADENOVIRUS-MEDIATED OVEREXPRESSION OF THE TRANSCRIPTION FACTOR E2F-1 INDUCES APOPTOSIS IN HUMAN BREAST AND OVARIAN-CARCINOMA CELL-LINES ANDDOES NOT REQUIRE P53

Apoptosis is a mode of cell death that is carefully regulated based on cellular and environmental signals, The ability to modulate the indiv idual cellular machinery and thereby to promote apoptosis is an import ant strategy in cancer therapy, It has previously been shown that over expression of the transcription factor E2F-1 can induce apoptosis in q uiescent rat embryo fibroblasts, This effect has been reported to occu r in a p53-dependent manner. To investigate whether overexpression of E2F-1 could also induce apoptosis in human cancer cells, a recombinant adenovirus vector containing the transgene E2F-1 under control of the cytomegalovirus promoter (Ad5CMVE2F) was used to induce high levels o f the E2F-1 protein in human breast and ovarian carcinoma cell lines, Significant morphological changes occurred in four of the five cell li nes within 48 h of transduction with the Ad5CMVE2F. These changes were consistent with apoptosis, which was confirmed further by DNA fragmen tation assay and fluorescence-activated cell sorting analysis, On the basis of these assays, which show that apoptosis occurred in those cel l lines with mutations in the p53 gene, we suggest that the induction of E2F-1-mediated apoptosis does not require wild-type p53 when E2F-1 is overexpressed using an adenovirus-based strategy.