Role of the Chemokine MCP-1 in Sensitization of PKC-Mediated Apoptosis in Prostate Cancer Cells
Abstract
We have established that PKC isozymes are important regulators of the synthesis and release of death factors in prostate cancer cells. In response to phorbol ester treatment, LNCaP cells promote the release of TNFalpha, TRAIL, and MCP-1/CCL2. Our recent studies revealed that all three factors contribute to the apoptotic effect of phorbol esters in prostate cancer cells. We established that PKCalpha and PKCdelta mediate the sensitizing effect of CCL2. We also found that unlike PKCdelta, PKCepsilon has a pro-survival role in LNCaP cells. It is unclear yet whether PKCepsilon modulates the synthesis and/or release of death factors. Finally, we established that androgens modulate the synthesis and release of pro-apoptotic cytokines from LNCaP cells. Androgen depletion or androgen receptor RNAi markedly impacted the apoptotic effect of death factors as well as the activation of p38 MAPK and JNK pathways.
Document Details
- Document Type
- Technical Report
- Publication Date
- Feb 01, 2009
- Accession Number
- ADA500950
Entities
People
- Marcelo G Kazanietz
Organizations
- University of Pennsylvania