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

Noa Rotem-Dai, Galia Oberkovitz, Sara Abu-Ghanem, Etta Livneh

Research output: Contribution to journalArticlepeer-review

27 Scopus citations

Abstract

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, PKCη, 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 PKCη 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 PKCη. 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 PKCη expression. Hence, in contrast to most PKC isoforms enhancing JNK activation, our studies show that PKCη is an anti-apoptotic protein, acting as a negative regulator of JNK activity. Thus, PKCη could represent a target for intervention aimed to reduce resistance to anti-cancer treatments.

Original languageEnglish
Pages (from-to)2616-2623
Number of pages8
JournalExperimental Cell Research
Volume315
Issue number15
DOIs
StatePublished - 10 Sep 2009

Keywords

  • Apoptosis
  • Camptothecin
  • Caspases
  • Cytochrome c
  • DNA damage
  • JNK activity
  • MCF-7
  • PKCη
  • UVC irradiation
  • c-Jun

ASJC Scopus subject areas

  • Cell Biology

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