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Effect of a short CAG (glutamine) repeat on human androgen receptor function
Author(s) -
Ding Dacheng,
Xu Lihua,
Me Mani,
Reddy G. Prem Veer,
Barrack Evelyn R.
Publication year - 2003
Publication title -
the prostate
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.295
H-Index - 123
eISSN - 1097-0045
pISSN - 0270-4137
DOI - 10.1002/pros.10316
Subject(s) - transactivation , androgen receptor , prostate cancer , du145 , androgen , biology , population , endocrinology , cancer research , medicine , transfection , cancer , gene , genetics , gene expression , lncap , hormone , environmental health
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. © 2003 Wiley‐Liss, Inc.