Overexpression of protein kinase C-η attenuates caspase activation and tumor necrosis factor-α-induced cell death

The protein kinase C (PKC) signal transduction pathway regulates cell death by tumor necrosis factor-α (TNF). We previously showed that the induction of novel PKCη isozyme by PKC activators correlated with their ability to protect MCF-7 breast cancer cells against TNF cytotoxicity. In the present study, we have transfected PKCη in MCF-7 cells to directly examine its involvement in cell death by TNF. Overexpression of PKCη delayed TNF-induced cell death in MCF-7 cells. TNF caused a rapid activation of caspase-8 and -7 in cells transfected with a vector. The activation of these caspases was potentiated by the PKC inhibitor bisindolylmaleimide (BIM) which downregulates PKCη and sensitizes cells to TNF. Overexpression of PKCη delayed the activation of caspase-8 and -7 by both TNF and the combination of BIM and TNF. These results suggest that PKCη protects MCF-7 cells against TNF-induced cell death by preventing the activation of caspases. (C) 2000 Academic Press.