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Adenovirus-Mediated Overexpression of the Transcription Factor E2F-1 Induces Apoptosis in Human Breast and Ovarian Carcinoma Cell Lines and Does Not Require p53¹

Departments of Surgical Oncology [K. K. H., M. W-H., M-C. H.], Tumor Biology [J. D., T-J. L., M-C. H.], Thoracic and Cardiovascular Surgery [S. G. S.], and Head and Neck Surgery [T-J. L., G. C.], The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030

Apoptosis is a mode of cell death that is carefully regulated based on cellular and environmental signals. The ability to modulate the individual cellular machinery and thereby to promote apoptosis is an important strategy in cancer therapy. It has previously been shown that overexpression of the transcription factor E2F-1 can induce apoptosis in quiescent rat embryo fibroblasts. This effect has been reported to occur 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 of the E2F-1 protein in human breast and ovarian carcinoma cell lines. Significant morphological changes occurred in four of the five cell lines within 48 h of transduction with the Ad5CMVE2F. These changes were consistent with apoptosis, which was confirmed further by DNA fragmentation assay and fluorescence-activated cell sorting analysis. On the basis of these assays, which show that apoptosis occurred in those cell 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.

¹ This work was supported by the M. D. Anderson Cancer Center Breast Cancer Research Program and Army Breast Cancer Grant DAMD 17-94-J4315 (to M-C. H.), M. D. Anderson Cancer Center Core Grant CA 16672, and NIH Training of Academic Surgical Oncologists Grant CA 09599.

² To whom requests for reprints should be addressed, at Breast Cancer Basic Science Research Program, Department of Tumor Biology, The University of Texas M. D. Anderson Cancer Center, Box 79, 1515 Holcombe Boulevard, Houston, TX 77030. Phone: (713) 792-3668; Fax: (713) 794-4784.

Received 6/26/97. Accepted 9/22/97.

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