PKC Epsilon: A Novel Oncogenic Player in Prostate Cancer
Annual summary rept. 1 Aug 2012-31 Aug 2013
PENNSYLVANIA UNIV PHILADELPHIA DEPT OF PHARMACOLOGY
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Protein kinase C epsilon PKCe, a member of the PKC family of phorbol esterdiacylglycerol receptors, is up-regulated in many human cancers, including prostate cancer. We recently demonstrated that PKCe is an essential mediator of NF-kB activation in prostate cancer Garg et al., JBC, 287, 37570 37582, 2012. In this research, we wish to determine if PKCe regulates TNFa-signaling to mediate its effect on NF-kB activation. Using a specific PKCe antagonist, we demonstrated that PKCe plays essential role in the TNFa-induced phosphorylation of TNF receptor in prostate cancer cells. We have previously identified that PKCe regulates NF-kB responsive genes in prostate cancer cells, including cyclooxygenase-2 COX-2 JBC, 2012. COX-2 has been reported to be up-regulated in metastatic prostate cancer. As PKCe plays an important role in prostate cancer cell survival and cooperates with other oncogenic insults, herein we aim to determine if PKCe regulates COX-2 activation during prostate tumorigenesis. We observe that PKCe RNAi depletion diminishes constitutive and stimulated COX-2 mRNA expression and PGE2 levels in prostate cancer cells. Conversely, PKCe overexpression by adenoviral means potentiates COX-2 expression in LNCaP cells. Thus, our study characterizes a novel molecular link between PKCe and NF-kBCOX-2 and its implication in survival pathways in prostate cancer.
- Medicine and Medical Research