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 (PC3-AR). PKCα was essentially cytoplasmic whereas PKCβ and PKCɛ were essentially membranal, suggesting their constitutive activity in the PC3-AR cells. Melatonin treatment induced membrane association of PKCα in a time and dose dependent manner. The PKCα and PKCβ1 specific inhibitor GO6976 and the PKCβ 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 PKCα activation is a critical step in AR nuclear exclusion by melatonin. They also imply that PKCα-activation is a potentially effective way to control of the AR activity in prostate cancer cells.