Vindrieux David, Réveiller Marie, Florin Anne, Blanchard Cécile, Ruffion Alain, Devonec Marian, Benahmed Mohamed, Grataroli Renée
Institut National de la Santé et de la Recherche Médicale, Communications Cellulaires en Biologie de la Reproduction, Faculté de Médecine Lyon-Sud, Oullins Cedex, France.
J Cell Physiol. 2006 Mar;206(3):709-17. doi: 10.1002/jcp.20520.
The apoptotic cell death process in the prostate is known to be under the control of androgens. Tumor necrosis factor-alpha (TNF-alpha)-related apoptosis-inducing ligand (TRAIL) is a member of the TNF-alpha family of cytokines, known to induce apoptosis upon binding to its death domain-containing receptors, DR4/TRAIL-R1 and DR5/TRAIL-R2. Two additional TRAIL receptors, DcR1/TRAIL-R3 and DcR2/TRAIL-R4, lack functional death domains and act as decoy receptors for TRAIL. In this study, we examined whether TRAIL and cellular receptors expression was targeted by androgens during the apoptotic cell death process in the hormone sensitive ventral prostate. The role of androgens was investigated using two sets of experiment. (1) Androgen deprivation associated with an apoptotic process resulted in a decrease in DcR2 mRNA and protein expression in the ventral prostate 3 days after castration. Testosterone administration to castrated adult rats prevented the decrease in DcR2 mRNA and protein levels in the ventral prostate. In contrast, DcR2 expression was modified, neither in the dorsolateral nor in the anterior prostate following castration. No changes were observed in DR4, DR5, DcR1, and TRAIL mRNA and protein levels in prostate after castration. (2) A specific decrease in DcR2 expression was observed in the ventral prostate after treatment of rats with the anti-androgen flutamide. Together, the present results suggest that testosterone specifically controls DcR2 expression in the adult rat ventral prostate. Androgen withdrawal, by reducing DcR2 expression, might leave the cells vulnerable to cell death signals generated by TRAIL via its functional receptors.
已知前列腺中的凋亡细胞死亡过程受雄激素调控。肿瘤坏死因子-α（TNF-α）相关凋亡诱导配体（TRAIL）是TNF-α细胞因子家族的成员，已知其与含死亡结构域的受体DR4/TRAIL-R1和DR5/TRAIL-R2结合后可诱导凋亡。另外两种TRAIL受体，DcR1/TRAIL-R3和DcR2/TRAIL-R4，缺乏功能性死亡结构域，可作为TRAIL的诱饵受体。在本研究中，我们检测了在激素敏感的腹侧前列腺凋亡细胞死亡过程中，雄激素是否靶向作用于TRAIL及其细胞受体的表达。通过两组实验研究了雄激素的作用。（1）与凋亡过程相关的雄激素剥夺导致去势后3天腹侧前列腺中DcR2 mRNA和蛋白表达下降。给去势成年大鼠注射睾酮可防止腹侧前列腺中DcR2 mRNA和蛋白水平下降。相比之下，去势后背外侧前列腺和前叶前列腺中的DcR2表达均未改变。去势后前列腺中DR4、DR5、DcR1和TRAIL的mRNA和蛋白水平未观察到变化。（2）用抗雄激素氟他胺处理大鼠后，腹侧前列腺中观察到DcR2表达特异性降低。总之，目前的结果表明睾酮特异性地控制成年大鼠腹侧前列腺中DcR2的表达。雄激素撤退通过降低DcR2表达，可能使细胞易受TRAIL通过其功能性受体产生的细胞死亡信号的影响。
