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.

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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.

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©1995 American Association for Cancer Research.
1995
American Association for Cancer Research, Inc.