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- Title
Protein kinase C? interacts with Bax and promotes survival of human prostate cancer cells.
- Authors
McJilton, Meagan A.; Van Sikes, C.; Wescott, Ginger G.; Daqing Wu; Gregory, Christopher W.; Weidner, Douglas A.; Ford, O. Harris; Lasater, A. Morgan; Mohler, James L.; Terrian, David M.; Foreman, Tonia L.
- Abstract
Prostatic glandular epithelial cells express protein kinase C? (PKC?), an oncoprotein that coordinately disrupts the reactivation of the tumor suppressor Rb, derepressess transcriptional elongation of the c-myc oncogene, and propagates survival signals in LNCaP cells. Since the activation of such a program may contribute to the progression of human prostate cancer, a proteomic analysis was performed to gain a more global perspective on the signaling network that PKC? might be capable of engaging in prostate cancer cells. Using CWR22 xenografts, we identified at least 18 different structural, signaling, and stress-related proteins that associated with PKC?, including an interaction with the proapoptotic protein Bax that was novel to recurrent CWR22 tumors. An investigation into the biological significance of the PKC? association with Bax provided the first evidence of an inverse relationship between endogenous levels of PKC? and susceptibility of prostate cancer cells to the apoptotic effects of phorbol esters. Western blot and antisense experiments demonstrated that CWR-R1 cells expressed moderate levels of PKC? and relied on this protein to survive in the presence of phorbol esters, while the apoptosis normally induced by phorbol esters in PKC?-deficient LNCaP cells was dependent on the presence of Bax. Forced expression of PKC? in LNCaP cells was sufficient to confer a significant resistance to phorbol esters and this resistance was associated with an inhibition of phorbol ester-induced Bax conformational rearrangements that are important for Bax oligomerization, mitochondrial integration, and cytochrome c release. Considered in their entirety, our data suggest that an association of PKC? with Bax may neutralize apoptotic signals propagated through a mitochondrial death-signaling pathway.Oncogene (2003) 22, 6014-6024. doi:10.1038/sj.onc.1206795
- Subjects
EPITHELIAL cells; EPITHELIUM; CELLS; PROTEIN kinase C; MYC oncogenes; XENOGRAFTS; PROSTATE cancer
- Publication
Oncogene, 2003, Vol 22, Issue 39, p6014
- ISSN
0950-9232
- Publication type
Article
- DOI
10.1038/sj.onc.1206795