Role of protein kinase Cα in melatonin signal transduction

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 (PO-AR). PKC alpha was essentially cytoplasmic whereas PKC beta and PKCs were essentially membranal, suggesting their constitutive activity in the PO-AR cells. Melatonin treatment induced membrane association of PKC alpha in a time and dose dependent manner. The PKC alpha and PKC beta 1 specific inhibitor GO6976 and the PKC beta 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 PKC alpha activation is a critical step in AR nuclear exclusion by melatonin. They also imply that PKC alpha-activation is a potentially effective way to control of the AR activity in prostate cancer cells. (c) 2006 Elsevier Ireland Ltd. All rights reserved.