title: Establishment and characterization of an androgen receptor-dependent, androgen-independent human prostate cancer cell line, LNCaP-CS10.
abstract: BACKGROUND
  Hormone refractoriness is a lethal event for advanced prostate cancer patients, but the mechanisms of the disease are not well elucidated, especially for the so-called "outlaw" pathways of androgen receptor (AR)-dependent, androgen-independent hormone-refractory prostate cancer.
  
  
  METHODS
  Androgen-dependent prostate cancer LNCaP cells were treated with bicalutamide under an androgen-depleted condition to obtain refractory cells. In the obtained cell line, LNCaP-CS10, we analyzed the effects of androgen and bicalutamide on cell growth and prostate-specific antigen (PSA) production. In addition, AR gene mutation, AR expression levels, and AR subcellular localizations were analyzed.
  
  
  RESULTS
  In LNCaP-CS10, cell growth and PSA production were found under an androgen-depleted condition and were induced by both R1881 and bicalutamide. Knocking down AR by siRNAs did suppress the growth and PSA production of LNCaP-CS10 cells in the androgen-depleted condition. In comparison to LNCaP, amplification or additional new mutations were not found in the AR genes, but AR nuclear translocation induced by bicalutamide was identified in the LNCaP-CS10 cells. The growth and PSA production of xenografted LNCaP-CS10 tumors, which secrete PSA not only in non-castrated SCID mice but also in castrated SCID mice, were not inhibited by bicalutamide.
  
  
  CONCLUSIONS
  We have generated a bicalutamide-resistant and androgen-independent prostate cancer cell line, LNCaP-CS10, with outlaw activation both in vitro and in vivo. The LNCaP-CS10 cell line is beneficial for elucidating outlaw pathway mechanisms and evaluating the efficacy of new therapeutics for hormone-refractory prostate cancer.
authors.affiliation: Research Division, Kamakura Research Laboratories, Pharmaceutical Research Department 2, Chugai Pharmaceutical Co. Ltd., Kamakura, Kanagawa, Japan. ishikuranby@chugai-pharm.co.jp
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Ishikura
authors.forename: Hiromitsu
authors.initials: H
authors.lastname: Kawata
authors.forename: Ayako
authors.initials: A
authors.lastname: Nishimoto
authors.forename: Ryo
authors.initials: R
authors.lastname: Nakamura
authors.forename: Nobuya
authors.initials: N
authors.lastname: Ishii
authors.forename: Yuko
authors.initials: Y
authors.lastname: Aoki
mesh_terms: D000813:Anilides / Q000494:pharmacology*; D000818:Animals; D045744:Cell Line, Tumor; D019008:Drug Resistance, Neoplasm; D006801:Humans; D008297:Male; D051379:Mice; D016513:Mice, SCID; D009570:Nitriles / Q000494:pharmacology*; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000473:pathology*; D011944:Receptors, Androgen / Q000502:physiology*; D019947:Receptors, Interleukin-6 / Q000502:physiology; D014105:Tosyl Compounds / Q000494:pharmacology*
chemical_list: D000813:Anilides; D009570:Nitriles; D011944:Receptors, Androgen; D019947:Receptors, Interleukin-6; D014105:Tosyl Compounds; C053541:bicalutamide; D017430:Prostate-Specific Antigen