Overexpression of Bcl-XS sensitizes MCF-7 cells to chemotherapy-induced apoptosis
Sumantran, V.N.; Ealovega, M.W.; Nuñez, G.; Clarke, M.F.; Wicha, M.S.
Cancer Research 55(12): 2507-2510
1995
ISSN/ISBN: 0008-5472 PMID: 7780958 Document Number: 441501
Resistance to apoptosis plays an important role in tumors that are refractory to chemotherapy. We report that Bcl-x-L, which functions like Bcl-2 to inhibit apoptosis, is highly expressed in MCF-7 human breast carcinoma cells. We used Bcl-x-s, a dominant negative inhibitor of Bcl-2 and BCl-x-L, to demonstrate the role of these genes in modulating chemotherapy-induced apoptosis. Bcl-x-s 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.