Alterations of androgen receptor in prostate cancer

被引:103
作者
Linja, MJ
Visakorpi, T
机构
[1] Univ Tampere, Canc Genet Lab, Inst Med Technol, FIN-33520 Tampere, Finland
[2] Tampere Univ Hosp, FIN-33520 Tampere, Finland
基金
芬兰科学院;
关键词
prostate cancer; androgen receptor; AR; amplification; mutation; predisposition; polymorphism;
D O I
10.1016/j.jsbmb.2004.10.012
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The significance of androgens in the development of prostate cancer has been known for more than half century. During the last decade, a lot of effort has been put to study the significance of the specific nuclear receptor of the hormone, androgen receptor (AR). It has been suggested that polymorphisms, especially the length of CAG repeat in exon I of the gene, are associated with the risk of prostate cancer. However, not all studies have confirmed the association. Most surprisingly, it has now become clear that prostate carcinomas emerging during the androgen withdrawal therapy (i.e. hormone-refractory tumors) are capable of reactivating the AR-mediated signalling despite of the low levels of androgens. In addition, it has been shown that AR gene itself is genetically targeted. One-third of the hormone-refractory prostate carcinomas contains amplification of the gene. In addition, 10-30% of prostate carcinomas treated by antiandrogens acquire point mutation in the AR gene. The genetic alterations in AR indicate that receptor should be considered as putative treatment target. Evidently, the currently available antiandrogens are not capable to abolish the AR-mediated signalling efficiently enough. (C) 2004 Elsevier Ltd. All rights reserved.
引用
收藏
页码:255 / 264
页数:10
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