OBJECTIVE: The function and significance of estrogen receptor β (ERβ) in bladder cancer remains a field of hot debate.
In this study, we aimed to (a) evaluate ERβ as a novel prognostic marker of recurrence-free survival and (b) digest the underlying mechanism by elucidating the relationship between ERβ expression and cadherin switch.
METHODS: We examined the expression levels of ERβ, E-cadherin and N-cadherin in 42 initial non-muscle-invasive urothelial bladder carcinomas via immunohistochemistry. Correlation analysis was performed among ERβ 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 ERβ-selective agonist diarylpropionitrile, E-cadherin, N-cadherin expressions; cell migration, and invasion capacity were assessed.
RESULTS: Expression of ERβ 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). ERβ expression and the non-cadherin switch are both accompanied with better recurrence-free survival. Also, the least ERβ 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.
CONCLUSION: ERβ 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.
Written by:
Han B, Cui D, Jing Y, Hong Y, Xia S. Are you the author?
Department of Urology, School of Medicine, The First People's Hospital Affiliated to Shanghai Jiao Tong University, Shanghai, People's Republic of China.
Reference: World J Urol. 2012 Jan 12. [Epub ahead of print]
PubMed Abstract
PMID: 22238119
UroToday.com Investigational Urology Section