Role of the Chemokine MCP-1 in Sensitization of PKC-Mediated Apoptosis in Prostate Cancer Cells

摘要

Our studies identified a novel paradigm by which PKC activation drives apoptotic responses in prostate cancer cells, which involves the autocrine release of TNFalpha TRAIL, and MCP-1 (CCL2). MCP-1(CCL2) sensitizes the death effect of other cytokines through a PKC-dependent pathway. Phorbol esters control the expression and release of these cytokines/chemokines from prostate cancer cells. These effects are primarily mediated by PKCalpha and PKCdelta. On the other hand, PKCepsilon opposes these effects, and confer protection for apoptosis. Our studies also identified an important role for androgens in the control of the secretion of cytokines/chemokines from prostate cancer cells.