Overexpression of protein kinase C-eta attenuates caspase activation and tumor necrosis factor-alpha-induced cell death.
The protein kinase C (PKC) signal transduction pathway regulates cell death by tumor necrosis factor-alpha (TNF). We previously showed that the induction of novel PKC eta 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 PKC eta in MCF-7 cells to directly examine its involvement in cell death by TNF. Overexpression of PKC eta 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 PKC eta and sensitizes cells to TNF. Overexpression of PKC eta delayed the activation of caspase-8 and -7 by both TNF and the combination of BIM and TNF. These results suggest that PKC eta protects MCF-7 cells against TNF-induced cell death by preventing the activation of caspases.
Akkaraju
G R
GR
Department of Molecular Biology and Immunology, University of North Texas Health Science Center, Fort Worth, Texas 76107, USA.
Basu
A
A
D053179:Caspase 7; D053181:Caspase 8; D053453:Caspase 9; D020169:Caspases / Q000378:metabolism*; D016923:Cell Death / Q000187:drug effects*; D004789:Enzyme Activation; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism*; D011493:Protein Kinase C / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D007527:Isoenzymes; D014409:Tumor Necrosis Factor-alpha; C081975:protein kinase C eta; D011493:Protein Kinase C; C505520:CASP7 protein, human; C505530:CASP8 protein, human; C506433:CASP9 protein, human; D053179:Caspase 7; D053181:Caspase 8; D053453:Caspase 9; D020169:Caspases