Sampson S R, Lupowitz Z, Braiman L, Zisapel N
Faculty of Life Sciences, Gonda-Goldschmied Center, Bar-Ilan University, Ramat-Gan, Tel Aviv, Israel.
Mol Cell Endocrinol. 2006 Jun 27;252(1-2):82-7. doi: 10.1016/j.mce.2006.03.033. Epub 2006 May 12.
Melatonin induces nuclear exclusion of the androgen receptor (AR) via activation of protein kinase C (PKC). The specific members of the PKC superfamily involved in AR nuclear exclusion were investigated in prostate cancer PC3 cells stably transfected with the wild-type androgen receptor (PC3-AR). PKCalpha was essentially cytoplasmic whereas PKCbeta and PKCepsilon were essentially membranal, suggesting their constitutive activity in the PC3-AR cells. Melatonin treatment induced membrane association of PKCalpha in a time and dose dependent manner. The PKCalpha and PKCbeta1 specific inhibitor GO6976 and the PKCbeta isoform-specific inhibitor hispidin had no effects on AR localization under basal conditions. However, GO6976 but not hispidin negated the melatonin-mediated nuclear exclusion of the AR. These data indicate that PKCalpha activation is a critical step in AR nuclear exclusion by melatonin. They also imply that PKCalpha-activation is a potentially effective way to control of the AR activity in prostate cancer cells.
褪黑素通过激活蛋白激酶C（PKC）诱导雄激素受体（AR）的核排除。在稳定转染野生型雄激素受体的前列腺癌PC3细胞（PC3-AR）中，研究了参与AR核排除的PKC超家族的特定成员。PKCα主要位于细胞质中，而PKCβ和PKCε主要位于细胞膜上，表明它们在PC3-AR细胞中具有组成性活性。褪黑素处理以时间和剂量依赖性方式诱导PKCα的膜结合。PKCα和PKCβ1特异性抑制剂GO6976以及PKCβ亚型特异性抑制剂漆黄素在基础条件下对AR定位没有影响。然而，GO6976而非漆黄素消除了褪黑素介导的AR核排除。这些数据表明PKCα激活是褪黑素诱导AR核排除的关键步骤。它们还暗示PKCα激活是控制前列腺癌细胞中AR活性的潜在有效方法。
