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Departments of Internal Medicine [V. N. S., M. W. E., M. F. C., M. S. W.] and Pathology [G. N.], University of Michigan Comprehensive Cancer Center, Ann Arbor, Michigan 48109-0724
Resistance to apoptosis plays an important role in tumors that are refractory to chemotherapy. We report that Bcl-xL, which functions like Bcl-2 to inhibit apoptosis, is highly expressed in MCF-7 human breast carcinoma cells. We used Bcl-xS, a dominant negative inhibitor of Bcl-2 and Bcl-xL, to demonstrate the role of these genes in modulating chemotherapy-induced apoptosis. Bcl-xS overexpressed in MCF-7 cells by stable transfection does not affect viability by itself but induces a marked increase in chemosensitivity to VP-16 or taxol. Using an ELISA assay which quantitates DNA damage, we demonstrate that this sensitization is due to apoptosis, suggesting the therapeutic utility of targeting this pathway.
1 This research was supported by NIH Grants CA-61777 and CA-64556, and American Cancer Society Grant BE-161C. G. N. is supported by NIH Research Career Development Award K04 CA64421-01.
2 To whom requests for reprints should be addressed, at Department of Internal Medicine, University of Michigan Comprehensive Cancer Center, 102 Observatory Street, Ann Arbor, MI 48109-0724.
Received 3/ 1/95. Accepted 4/21/95.
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