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bcl-x_s Gene Therapy Induces Apoptosis of Human Mammary Tumors in Nude Mice¹

Department of Internal Medicine, University of Michigan Comprehensive Cancer Center, Ann Arbor, Michigan 48109-0724

Bcl-x_s is a dominant negative repressor of Bcl-2 and Bcl-x_L, both of which inhibit apoptosis. We used a replication-deficient adenoviral vector to transiently overexpress Bcl-x_s in MCF-7 human breast cancer cells, which overexpress Bcl-x_L. Infection with this vector induced apoptosis in vitro. We then determined the effects of intratumoral injection of bcl-x_s adenovirus on solid MCF-7 tumors in nude mice. Tumors injected four times with the bcl-x_s adenovirus showed a 50% reduction in size. Using terminal transferase-mediated dUTP-digoxigenin nick end labeling, we observed apoptotic cells at sites of bcl-x_s adenoviral injection. These experiments demonstrate the feasibility of using bcl-x_s gene therapy to induce apoptosis in human breast tumors.

¹ This research was supported by NIH Grants CA-61777 and CA-64556 and American Cancer Society Grant BE-161C.

² To whom requests for reprints should be addressed, at University of Michigan Comprehensive Cancer Center, 102 Observatory Street, Ann Arbor, MI 48109-0724.

Received 1/18/96. Accepted 3/15/96.

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