Effect of a short CAG (glutamine) repeat on human androgen receptor functin

被引:69
作者
Ding, DC
Xu, LH
Menon, M
Reddy, GPV
Barrack, ER
机构
[1] Vattikuti Urol Inst, Henry Ford Hlth Sci Ctr, Detroit, MI 48202 USA
[2] Henry Ford Hosp, Vattikuti Urol Inst, Detroit, MI 48202 USA
关键词
polymorphism; prostate cancer; transactivation; immunoblot; alleles;
D O I
10.1002/pros.10316
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
BACKGROUND. The human androgen receptor (AR) gene contains an uninterrupted CAG repeat that is polymorphic in length in the general population (range, 11-31 CAG's; median, 21). The CAG repeat encodes a glutamine repeat in the N-terminal transactivation domain of the AR protein. We previously reported that a 17-CAG AR gene was much more common in a cohort of men with prostate cancer (8.5%) than in the general European American population (1.3%). This suggested that a 17-CAG repeat may have pathophysiological consequences. The goal of the present study was to directly test the hypothesis that a 17-CAG repeat might uniquely affect androgen action in human prostate cancer cells. METHODS. DU145 cells, lacking endogenous AR, were transiently transfected with an AR expression plasmid (with a CAG repeat ranging in length from 14 to 25) and an androgen-responsive reporter plasmid (PSA-luciferase). RESULTS. We found a significant effect of CAG repeat length on AR protein levels per unit amount of DNA transfected (one-way ANOVA, P = 0.02), indicating the need to express transactivation data per unit amount of AR protein. CAG17 AR had 40% more transactivation activity per unit amount of AR protein than CAG21 AR (P < 0.01). CONCLUSIONS. Thus, an AR with a 17-CAG repeat may mediate more efficacious growth stimulation of androgen-dependent prostate epithelial cells, and thereby increase the risk that prostate cancer cells develop more efficiently into a clinically significant cancer. (C) 2004 Wiley-Liss, Inc.
引用
收藏
页码:23 / 32
页数:10
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