title: Androgen receptor signaling regulates cell growth and vulnerability to doxorubicin in bladder cancer.
abstract: OBJECTIVE
  There are several reports of androgen receptor in bladder cancer cases but androgen receptor expression and the function of androgen/androgen receptor signaling in bladder cancer remain unclear. We investigated androgen receptor expression and the role of androgen/androgen receptor signaling in bladder cancer.
  
  
  METHODS
  We evaluated AR mRNA expression in bladder cancer tissue by quantitative real-time polymerase chain reaction. The role of androgen receptor in cell growth and drug sensitivity was also evaluated in vitro and in vivo in several bladder cancer cell lines.
  
  
  RESULTS
  AR mRNA expression inversely correlated with bladder cancer grade, stage and spread. Of several bladder cancer cell lines UMUC3 and MBT-2 markedly expressed androgen receptor transcript and protein. In each cell line androgen/androgen receptor signaling blockade using androgen deprivation, blockade knockdown and antiandrogen agents decreased cell growth, colony formation and cell viability. Androgen receptor expression was implicated in doxorubicin resistance. Inversely androgen receptor deprivation and knockdown made UMUC3 cells sensitive to doxorubicin. Finally, castration slightly suppressed UMUC3 tumor growth in vivo, although this did not attain statistical significance.
  
  
  CONCLUSIONS
  AR transcript expression inversely correlates with bladder cancer clinicopathological characteristics. Androgen/androgen receptor signaling has an important role in the growth and vulnerability to doxorubicin of bladder cancer cells that express androgen receptor. Androgen/androgen receptor signaling might be a possible prophylactic and therapeutic target for bladder cancer that shows androgen receptor expression.
authors.affiliation: Department of Urology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Masaki
authors.initials: M
authors.lastname: Shiota
authors.forename: Ario
authors.initials: A
authors.lastname: Takeuchi
authors.forename: Akira
authors.initials: A
authors.lastname: Yokomizo
authors.forename: Eiji
authors.initials: E
authors.lastname: Kashiwagi
authors.forename: Katsunori
authors.initials: K
authors.lastname: Tatsugami
authors.forename: Kentaro
authors.initials: K
authors.lastname: Kuroiwa
authors.forename: Seiji
authors.initials: S
authors.lastname: Naito
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000627:therapeutic use; D002453:Cell Cycle; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D015653:Cystectomy; D004317:Doxorubicin / Q000627:therapeutic use*; D005260:Female; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D051379:Mice; D008819:Mice, Nude; D008875:Middle Aged; D009374:Neoplasms, Experimental; D012334:RNA, Neoplasm / Q000235:genetics*; D060888:Real-Time Polymerase Chain Reaction; D011944:Receptors, Androgen / Q000096:biosynthesis / Q000235:genetics*; D012189:Retrospective Studies; D015398:Signal Transduction; D001749:Urinary Bladder Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000628:therapy
chemical_list: D000903:Antibiotics, Antineoplastic; D012334:RNA, Neoplasm; D011944:Receptors, Androgen; D004317:Doxorubicin