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[Cancer Research 60, 788-792, February 15, 2000]
© 2000 American Association for Cancer Research

Advances in Brief

Adenoviral Bak Overexpression Mediates Caspase-dependent Tumor Killing1

Abujiang Pataer, Bingliang Fang, Robert Yu, Shunsuke Kagawa, Kelly K. Hunt, Timothy J. McDonnell, Jack A. Roth and Stephen G. Swisher2

Section of Thoracic Molecular Oncology, Department of Thoracic and Cardiovascular Surgery [A. P., B. F., R. Y., S. K., J. A. R., S. G. S.] and Departments of Surgical Oncology [K. K. H] and Molecular Pathology [T. J. M.], The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030

One of the most promising strategies in cancer gene therapy is adenoviral transfer of proapoptotic genes. We therefore evaluated the novel strategy of adenovirally overexpressing the proapoptotic Bak gene. Our results showed marked apoptosis in cancer cells in vivo and in vitro after Bak gene transfer via a binary adenoviral vector system. This effect was not seen in a caspase 3-defective cell line (MCF-7) and was abrogated in Bak-sensitive tumors after administration of the caspase inhibitor z-DEVD-fmk. Our results suggest that adenoviral-mediated overexpression of Bak provides a novel therapeutic strategy for cancer therapy, but this process appears to be caspase dependent.




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