Abstract
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 PKCε 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.
Original language | English |
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Pages (from-to) | 82-87 |
Number of pages | 6 |
Journal | Molecular and Cellular Endocrinology |
Volume | 252 |
Issue number | 1-2 |
DOIs | |
State | Published - 27 Jun 2006 |
Keywords
- Androgen receptor
- Melatonin
- Prostate
- Protein kinase C