Role of the Chemokine MCP-1 in Sensitization of PKC-Medicated Apoptosis in Prostate Cancer Cells; Annual rept. 22 Jan 2007-21 Jan 2008

摘要

The main conclusion from the research in the first year of funding is that PKC isozymes play a role in the control of the release of death factors from prostate cancer cells. It is clear that PKCs control the expression of mRNA for death factors in prostate cancer cells and therefore there is great potential that PKC isozymes modulate either their transcription or mRNA stability. We succeeded in establishing the kinetics of CCL2 mRNA expression and release from LNCaP in prostate cancer cells in response to the phorbol ester PMA. We also found that CCL2 release occurs also in androgen-independent prostate cancer cells and that this effect is mediated by PKC alpha and PKC delta isozymes. We also established a role for p38 MAPK in the release of CCL2 from LNCaP cells induced by PMA. Importantly our research during the last year allowed to establish a novel paradigm which suggest that androgens regulate apoptotic factor release from prostate cancer cells in response to PKC activation.