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 253J. 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 253J cell lines studies. Diarylpropionitrile stimulation resulted in an increase in E-cadherin, a decrease in N-cadherin expression 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.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 / Q000378:metabolism*; D002295:Carcinoma, Transitional Cell / Q000378:metabolism / Q000401:mortality* / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement; D003131:Combined Modality Therapy; D015653:Cystectomy; D004358:Drug Therapy; D047629:Estrogen Receptor beta / Q000378:metabolism*; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000378:metabolism / Q000401:mortality* / Q000473:pathology; D011379:Prognosis; D015996:Survival Rate; D001749:Urinary Bladder Neoplasms / Q000378:metabolism / Q000401:mortality* / Q000473:pathology
chemical_list: D014408:Biomarkers, Tumor; D015820:Cadherins; D047629:Estrogen Receptor beta