PKCη confers protection against apoptosis by inhibiting the pro-apoptotic JNK activity in MCF-7 cells

Apoptosis is frequently regulated by different protein kinases including protein kinase C family enzymes. Both inhibitory and stimulatory effects were demonstrated for several of the different PKC isoforms. Here we show that the novel PKC isoform, PKC eta, confers protection against apoptosis induced by the DNA damaging agents, UVC irradiation and the anti-cancer drug-Camptothecin, of the breast epithelial adenocarcinoma MCF-7 cells. The induced expression of PKC eta in MCF-7 cells, under the control of the tetracycline-responsive promoter, resulted in increased cell survival and inhibition of cleavage of the apoptotic marker PARP-1. Activation of caspase-7 and 9 and the release of cytochrome c were also inhibited by the inducible expression of PKC eta. Furthermore, JNK activity, required for apoptosis in MCF-7, as indicated by the inhibition of both caspase-7 cleavage and cytochrome c release from the mitochondria in the presence of the JNK inhibitor SP600125, was also suppressed by PKC. expression. Hence, in contrast to most PKC isoforms enhancing JNK activation, our studies show that PKC eta is an anti-apoptotic protein, acting as a negative regulator of JNK activity. Thus, PKC. could represent a target for intervention aimed to reduce resistance to anti-cancer treatments. (C) 2009 Elsevier Inc. All rights reserved.