Relaxin becomes upregulated during prostate cancer progression to androgen independence and is negatively regulated by androgens.
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.
Thompson
Vanessa C
VC
The Prostate Centre, Vancouver General Hospital, Vancouver, British Columbia, Canada.
Morris
Tanis G W
TG
Cochrane
Dawn R
DR
Cavanagh
John
J
Wafa
Latif A
LA
Hamilton
Tatyana
T
Wang
Shunyou
S
Fazli
Ladan
L
Gleave
Martin E
ME
Nelson
Colleen C
CC
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
D045165:Testosterone Congeners; D015741:Metribolone; D012065:Relaxin