OVEREXPRESSION OF CATHEPSIN D SENZITIZES BREAST CANCER CELLS TO TRAIL-INDUCED APOPTOSIS
|Fakulta / Pracoviště MU
|Breast cancer cells overexpressing cathepsin D wt and mut were exposed to TRAIL and frequency of apoptosis was determined by chromatin condensation, nuclear fragmentation, cleavage of PARP, and externalization of phosphatidylserine. An increased frequency of apoptosis in cells over-expressing wt but not mut CTSD was clearly demonstrated. Increased frequency of apoptosis observed in wt CTSD cells corresponded to cleavage of the pro-apoptotic Bcl-2 family member, the Bid protein, that was earlier identified as one of the targets of CTSD in cancer cells. We conclude that CTSD sensitizes MDA-MB-231 cells to the TRAIL-induced apoptosis in enzymatic activity-dependent manner and that the TRAIL-induced apoptosis is potentiated by the CTSD-mediated activation of Bid, the pro-apoptotic member of the Bcl-2 family.