title: Relaxin becomes upregulated during prostate cancer progression to androgen independence and is negatively regulated by androgens.
abstract: BACKGROUND
  Relaxin is a potent peptide hormone normally secreted by the prostate. This study characterized relaxin expression during prostate cancer progression to androgen independence (AI), and in response to androgens.
  
  
  METHODS
  The prostate cancer cell line, LNCaP, was assayed by microarrays and confirmatory Northern analysis to assess changes in relaxin levels due to androgen treatment and in LNCaP xenografts following castration. Relaxin protein levels were examined by immunohistochemistry (IHC) in tissue microarrays of human prostate cancer samples following androgen ablation.
  
  
  RESULTS
  Relaxin levels decreased in a time and concentration-dependent manner due to androgens in vitro, and increased in xenografts post-castration. Relaxin increased in radical prostatectomy specimens after 6 months of androgen ablation and in AI tumors, was highest in bone metastases.
  
  
  CONCLUSIONS
  Relaxin is negatively regulated by androgens in vitro and in vivo, which correlates to clinical prostate cancer specimens following androgen ablation. The role of relaxin in angiogenesis and tissue remodeling suggests it may contribute to prostate cancer progression.
authors.affiliation: The Prostate Centre, Vancouver General Hospital, Vancouver, British Columbia, Canada.
authors.forename: Vanessa C
authors.initials: VC
authors.lastname: Thompson
authors.forename: Tanis G W
authors.initials: TG
authors.lastname: Morris
authors.forename: Dawn R
authors.initials: DR
authors.lastname: Cochrane
authors.forename: John
authors.initials: J
authors.lastname: Cavanagh
authors.forename: Latif A
authors.initials: LA
authors.lastname: Wafa
authors.forename: Tatyana
authors.initials: T
authors.lastname: Hamilton
authors.forename: Shunyou
authors.initials: S
authors.lastname: Wang
authors.forename: Ladan
authors.initials: L
authors.lastname: Fazli
authors.forename: Martin E
authors.initials: ME
authors.lastname: Gleave
authors.forename: Colleen C
authors.initials: CC
authors.lastname: Nelson
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D015536:Down-Regulation; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D015741:Metribolone / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009376:Neoplasms, Hormone-Dependent / Q000378:metabolism; D009919:Orchiectomy; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000628:therapy; D012065:Relaxin / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D045165:Testosterone Congeners / Q000494:pharmacology*; D015854:Up-Regulation; D023041:Xenograft Model Antitumor Assays
chemical_list: D045165:Testosterone Congeners; D015741:Metribolone; D012065:Relaxin