Rho/ROCK/actin signaling regulates membrane androgen receptor induced apoptosis in prostate cancer cells

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• 作者：Natalia Papadopoulou ; Ioannis Charalampopoulos ; Konstantinos Alevizopoulos ; Achille Gravanis ; Christos Stournaras
• 关键词：mAR activation ; Actin dynamics ; Rho-GTPase signaling ; Apoptosis ; Prostate cancer
• 刊名：Experimental Cell Research
• 出版年：2008
• 出版时间：15 October 2008
• 年：2008
• 卷：314
• 期：17
• 页码：3162-3174
• 全文大小：1900 K

文摘

In this study we describe a novel Rho small GTPase dependent pathway that elicits apoptotic responses controlled by actin reorganization in hormone-sensitive LNCaP- and hormone insensitive DU145-prostate cancer cells stimulated with membrane androgen receptor selective agonists. Using an albumin-conjugated steroid, testosterone-BSA, we now show significant induction of actin polymerization and apoptosis that can be reversed by actin disrupting agents in both cell lines. Testosterone-BSA triggered RhoA/B and Cdc42 activation in DU145 cells followed by stimulation of downstream effectors ROCK, LIMK2 and ADF/destrin. Furthermore, dominant-negative RhoA, RhoB or Cdc42 mutants or pharmacological inhibitors of ROCK inhibited both actin organization and apoptosis in DU145 cells. Activation of RhoA/B and ROCK was also implicated in membrane androgen receptor-dependent actin polymerization and apoptosis in LNCaP cells. Our findings suggest that Rho small GTPases are major membrane androgen receptor effectors controlling actin reorganization and apoptosis in prostate cancer cells.