title: Estrogen receptor β (ERβ) is a novel prognostic marker of recurrence survival in non-muscle-invasive bladder cancer potentially by inhibiting cadherin switch.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Urology, School of Medicine, The First People's Hospital Affiliated to Shanghai Jiao Tong University, Shanghai, People's Republic of China.
authors.forename: Bangmin
authors.initials: B
authors.lastname: Han
authors.forename: Di
authors.initials: D
authors.lastname: Cui
authors.forename: Yifeng
authors.initials: Y
authors.lastname: Jing
authors.forename: Yan
authors.initials: Y
authors.lastname: Hong
authors.forename: Shujie
authors.initials: S
authors.lastname: Xia
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism; D015820:Cadherins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D002295:Carcinoma, Transitional Cell / Q000175:diagnosis* / Q000378:metabolism / Q000401:mortality*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D047629:Estrogen Receptor beta / Q000819:agonists / Q000187:drug effects / Q000378:metabolism*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000175:diagnosis* / Q000378:metabolism / Q000401:mortality*; D009570:Nitriles / Q000494:pharmacology; D011379:Prognosis; D011422:Propionates / Q000494:pharmacology; D012189:Retrospective Studies; D015996:Survival Rate; D001749:Urinary Bladder Neoplasms / Q000175:diagnosis* / Q000378:metabolism / Q000401:mortality*; D019459:Urothelium / Q000378:metabolism / Q000473:pathology
chemical_list: C486182:2,3-bis(4-hydroxyphenyl)-propionitrile; D014408:Biomarkers, Tumor; D015820:Cadherins; D047629:Estrogen Receptor beta; D009570:Nitriles; D011422:Propionates