HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via ISI Web of Science (1) Google Scholar Articles by Teng, J. Articles by Bjorling, D. E PubMed PubMed Citation Articles by Teng, J. Articles by Bjorling, D. E

¹ Department of Surgical Sciences, School of Veterinary Medicine, University of Wisconsin, 2015 Linden Dr, Madison, Wisconsin 53706, USA² Division of Urology, Department of Surgery, School of Medicine and Public Health, University of Wisconsin, Madison, Wisconsin 53792, USA

(Correspondence should be addressed to D E Bjorling; Email: bjorlind{at}svm.vetmed.wisc.edu)

We reported previously that both subtypes of estrogen receptors, ER and ERβ, are expressed by human urothelial cells and mediate estrogen-induced cell proliferation in these cells. The aim of this study was to determine the extent to which each ER subtype contributes to urothelial cell proliferation and their possible involvement in the regulation of the cell cycle. We compared the expression of ER and ERβ mRNAs and protein quantitatively in primarily cultured human bladder urothelial cells obtained from six individuals with three immortalized urothelial (E6, E7, and UROtsa) and two bladder cancer cell lines (HTB-9 and T24). We found that all these cells express similar levels of ERβ, but immortalized and cancer cells express much higher amounts of ER than primary cells. Higher levels of ER mRNA were also observed in the biopsies of bladder transitional cell carcinoma compared with sample from the same bladder unaffected by tumor. Using the ER-selective agonist PPT, the ERβ-selective agonist DPN, and specific small interfering RNA against ER or ERβ, we found that ERβ predominantly mediates estrogen-induced G1/S transition and cell proliferation in the primary urothelial cells. By contrast, ER predominantly mediates estrogen-induced G1/S transition and cell proliferation in bladder cancer cell lines. Furthermore, we found that 17β-estradiol (E₂) rapidly induces phosphorylation of extracellular signal-regulated kinases, but U0126, a mitogen-activated protein kinase kinase (MEK) inhibitor, does not affect E₂-induced urothelial cell proliferation. E₂ up-regulated cyclin D1 and cyclin E expression in both the primary and bladder cancer cells, and the cancer cells have higher cyclin D1 and cyclin E expression during G0/G1 phases. Our data suggest that estrogen exerts its effects through different ER subtypes in urothelial cells. Increased expression of ER may contribute to early induction of cyclin D1 and cyclin E during the cell cycle in bladder cancer cells.