Estrogen receptor β (ERβ) is a novel prognostic marker of recurrence survival in non-muscle-invasive bladder cancer potentially by inhibiting cadherin switch

The function and significance of estrogen receptor beta (ER beta) in bladder cancer remains a field of hot debate. In this study, we aimed to (a) evaluate ER beta as a novel prognostic marker of recurrence-free survival and (b) digest the underlying mechanism by elucidating the relationship between ER beta expression and cadherin switch. We examined the expression levels of ER beta, E-cadherin and N-cadherin in 42 initial non-muscle-invasive urothelial bladder carcinomas via immunohistochemistry. Correlation analysis was performed among ER beta expression, cadherin switch, and recurrence-free survival. Moreover, in vitro studies were performed to validate the identified correlation using two bladder cancer cell lines RT4 and 253 J. Upon stimulation with an ER beta-selective agonist diarylpropionitrile, E-cadherin, N-cadherin expressions; cell migration, and invasion capacity were assessed. Expression of ER beta protein was seen in 34 bladder cancer cases (80.9%), and 21 (50%) specimens showed non-cadherin switch (positive E-cadherin and negative N-cadherin). ER beta expression and the non-cadherin switch are both accompanied with better recurrence-free survival. Also, the least ER beta expression was observed in specimens that undergo cadherin switch. Moreover, these results were consistent with our observations in bladder cancer RT4 and 253 J cell lines studies. Diarylpropionitrile stimulation resulted in an increase in E-cadherin, a decrease in N-cadherin expressions and abolished cell migration and invasion. ER beta is a prognostic marker of recurrence-free rate in non-muscle-invasive bladder cancer, potentially through suppressing cadherin switch, and may act as a potential target for bladder cancer therapy.