PKC Epsilon: A Novel Oncogenic Player in Prostate Cancer
Abstract
Protein kinase C epsilon (PKC epsilon), a member of the PKC family of phorbol ester/diacylglycerol receptors, is up-regulated in many human cancers, including prostate cancer. We recently demonstrated that PKC epsilon is an essential mediator of NF-kappa B activation in prostate cancer (Garg et al., JBC, 287, 3757037582, 2012). In this research, we wish to determine if PKC epsilon regulates TNF alpha-signaling to mediate its effect on NF-kappa B activation. Using a specific PKC epsilon antagonist, we demonstrated that PKC epsilon plays essential role in the TNF alpha-induced phosphorylation of TNF receptor in prostate cancer cells. We have previously identified that PKC epsilon regulates NF-kappaB 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 PKC epsilon plays an important role in prostate cancer cell survival and cooperates with other oncogenic insults, herein we aim to determine if PKC epsilon regulates COX-2 activation during prostate tumorigenesis. In the previous funding period we have demonstrated that PKC epsilon mediates the activation of COX-2, a well-known NF-kappaB responsive gene in prostate cancer and that COX-2 mediates PKC epsilon responses in prostate cancer. In the present report, we present our continued efforts on the in-depth determination of the role of PKC epsilon in COX-2 activation in prostate cancer and also to investigate if COX-2 is a potential mediator of PKC epsilon oncogenesis in prostate cancer, particularly in the context of Pten loss and to determine if COX-2 inhibition could also affect the signaling event in adenocarcinoma formed in the compound PKC epsilon; Pten mice.
Document Details
- Document Type
- Technical Report
- Publication Date
- Nov 01, 2015
- Accession Number
- AD1002984
Entities
People
- Rachana Garg
Organizations
- University of Pennsylvania