LNCaP公司
比卡鲁胺
雄激素受体
二氢睾酮
前列腺癌
雄烯二醇
内分泌学
内科学
雄激素
癌症研究
生物
雄激素剥夺疗法
抗雄激素
化学
医学
癌症
激素
脱氢表雄酮
作者
Atsushi Mizokami,Eitetsu Koh,Hiroshi Fujita,Yuji Maeda,Masayuki Egawa,Kiyoshi Koshida,Seijiro Honma,Evan T. Keller,Mikio Namiki
出处
期刊:Cancer Research
[American Association for Cancer Research]
日期:2004-01-15
卷期号:64 (2): 765-771
被引量:176
标识
DOI:10.1158/0008-5472.can-03-0130
摘要
Abstract Despite an initial response to androgen deprivation therapy, prostate cancer (PCa) progresses eventually from an androgen-dependent to an androgen-independent phenotype. One of the mechanisms of relapse is antiandrogen withdrawal phenomenon caused by mutation of 877th amino acid of androgen receptor (AR). In the present study, we established a method to measure the concentration of androstenediol (adiol) in prostate tissue. We found that adiol maintains a high concentration in PCa tissue even after androgen deprivation therapy. Furthermore, adiol is a stronger activator of mutant AR in LNCaP PCa cells and induces more cell proliferation, prostate-specific antigen (PSA) mRNA expression, and PSA promoter than dihydrotestosterone (DHT). Because antiandrogen, bicalutamide, blocked adiol activity in LNCaP cells, it was suggested that adiol effect was mediated through AR. However, high concentration of bicalutamide was necessary to block completely adiol activity. These effects were specific to LNCaP cells because adiol had less effect in PC-3 PCa cells transfected with wild-type AR than DHT and had similar effect in PC-3 cells transfected with mutant AR. The mechanism that adiol activates mutant AR in LNCaP cells did not result from the increased affinity to mutant AR or from AR’s association with coactivator ARA70. However, low concentration of adiol induced more AR nuclear translocation than DHT in LNCaP cells and not PC-3 cells transfected with AR. These results indicate that adiol may cause the progression of PCa even after hormone therapy.
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