Estrogen receptor beta (ER beta) mediates expression of beta-catenin and proliferation in prostate cancer cell line PC-3

Abstract

The aim of the present study was to characterize the mechanism underlying estrogen effects on the androgen-independent prostate cancer cell line PC-3. 17 beta-estradiol and the ER beta-selective agonist DPN, but not the ER alpha-selective agonist PPT, increased the incorporation of [methyl-H-3]thymidine and the expression of Cyclin D2, suggesting that ER beta mediates the proliferative effect of estrogen on PC-3 cells. In addition, upregulation of Cyclin D2 and incorporation of [methyl-H-3]thymidine induced by 17 beta-estradiol and DPN were blocked by the ER beta-selective antagonist PHTPP in PC-3 cells. Upregulation of Cyclin D2 and incorporation of [methyl-H-3]thymidine induced by DPN were also blocked by PKF118-310, a compound that disrupts beta-catenin-TCF (T-cell-specific transcription factor) complex, suggesting the involvement of beta-catenin in the estradiol effects in PC-3 cells. A diffuse immunostaining for non-phosphorylated beta-catenin was detected in the cytoplasm of PC-3 cells. Low levels of nonphosphorylated beta-catenin immunostaining were also detected near the plasma membrane and in nuclei. Treatment of PC-3 cells with 17 beta-estradiol or DPN markedly increased non-phosphorylated beta-catenin expression. These effects were blocked by pretreatment with the ER beta-selective antagonist PHTPP, PI3K inhibitor Wortmannin or AKT inhibitor MK-2206, indicating that ER beta-PI3K/AKT mediates non-phosphorylated beta-catenin expression. Cycloheximide blocked the DPN-induced upregulation of nonphosphorylated beta-catenin, suggesting de novo synthesis of this protein. In conclusion, these results suggest that estrogen may play a role in androgen-independent prostate cancer cell proliferation through a novel pathway, involving ER beta-mediated activation of beta-catenin. (C) 2016 Elsevier Ireland Ltd. All rights reserved.