Activation of estrogen receptor beta (ERβ) regulates the expression of N-cadherin, E-cadherin and β-catenin in androgen-independent prostate cancer cells

The aim of the present study was to investigate the impact of the activation of estrogen receptors on expression and localization of N-cadherin, E-cadherin and non-phosphorylated beta-catenin in androgen-independent prostate cancer cells (PC-3 and DU-145) and in human post pubertal prostate epithelial cells (PNT1A). Expression of N-cadherin was detected in PNT1A and PC-3 cells, but not in DU-145 cells. E-cadherin was detected only in DU-145 cells and beta-catenin was detected in all cells studied. N-cadherin and beta-catenin were located preferentially in the cellular membrane of PNT1A cells and in the cytoplasm of PC-3 cells. E-cadherin and beta-catenin were located preferentially in the cellular membrane of DU-145 cells. 17 beta-estradiol (E2) or the ER alpha-selective agonist PPT did not affect the content and localization of N-cadherin in PC-3 and PNT1A cells or E-cadherin in DU-145 cells. In PC-3 cells, ER beta-selective agonist DPN decreased the expression of N-cadherin. DPN-induced downregulation of N-cadherin was blocked by pretreatment with the ER beta-selective antagonist (PHTPP), indicating that ER beta 1 is the upstream receptor regulating the expression of N-cadherin. In DU-145 cells, the activation of ER beta 1 by DPN increased the expression of E-cadherin. Taken together, these results suggest that activation of is required to maintain an epithelial phenotype in PC-3 and DU-145 cells. The activation of ER beta 1 also increased the expression of beta-catenin in cytoplasm of PC-3 and in the cellular membrane of DU-145 cells. In conclusion, our results indicate differential expression and localization of N-cadherin, E-cadherin and beta-catenin in androgen independent prostate cancer cells. The reduction of N-cadherin content by activation of ER beta, exclusively observed in androgen-independent prostate cancer cells (PC-3), may be related to the activation of signaling pathways, such as the release of beta-catenin into the cytoplasm, translocation of beta-catenin to the nucleus and activation of gene transcription.