We have previously shown that protein kinase Cε (PKCε) acts as an antiapoptotic protein and protects breast cancer MCF-7 cells from tumor necrosis factor-α (TNF)-mediated apoptosis. In the present study, we have investigated the mechanism by which PKCε inhibits TNF-induced cell death. Overexpression of wild-type PKCε (WT-PKCε) in MCF-7 cells decreased TNF-induced mitochondrial depolarization. Depletion of Bax by small interfering RNA (siRNA) attenuated TNF-induced cell death. Overexpression of PKCε in MCF-7 cells decreased dimerization of Bax and its translocation to the mitochondria. Knockdown of PKCε using siRNA induced Bax dimerization and mitochondrial translocation. PKCε was coimmunoprecipitated with Bax in MCF-7 cells. These results suggest that PKCε mediates its antiapoptotic effect partly by preventing activation and translocation of Bax to the mitochondria.
- MCF-7 cells