Thompson Vanessa C, Morris Tanis G W, Cochrane Dawn R, Cavanagh John, Wafa Latif A, Hamilton Tatyana, Wang Shunyou, Fazli Ladan, Gleave Martin E, Nelson Colleen C
The Prostate Centre, Vancouver General Hospital, Vancouver, British Columbia, Canada.
Prostate. 2006 Dec 1;66(16):1698-709. doi: 10.1002/pros.20423.
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.
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.
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.
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.
松弛素是一种通常由前列腺分泌的强效肽类激素。本研究对前列腺癌进展至雄激素非依赖状态(AI)期间以及对雄激素反应时的松弛素表达进行了特征分析。
利用微阵列和验证性Northern分析对前列腺癌细胞系LNCaP进行检测,以评估雄激素处理及去势后LNCaP异种移植瘤中松弛素水平的变化。采用免疫组织化学(IHC)方法检测雄激素去除后人前列腺癌样本组织微阵列中的松弛素蛋白水平。
在体外,松弛素水平因雄激素作用呈时间和浓度依赖性降低,而去势后异种移植瘤中松弛素水平升高。雄激素去除6个月后,根治性前列腺切除标本及AI肿瘤中的松弛素水平升高,在骨转移瘤中最高。
在体外和体内,雄激素对松弛素起负调控作用,这与雄激素去除后的临床前列腺癌标本情况相关。松弛素在血管生成和组织重塑中的作用表明它可能促进前列腺癌进展。