title: Effect of a short CAG (glutamine) repeat on human androgen receptor function.
abstract: 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.
authors.affiliation: The Vattikuti Urology Institute, Henry Ford Hospital and Henry Ford Health Sciences Center, Detroit, Michigan 48202-3450, USA.
authors.forename: Dacheng
authors.initials: D
authors.lastname: Ding
authors.forename: Lihua
authors.initials: L
authors.lastname: Xu
authors.forename: Mani
authors.initials: M
authors.lastname: Menon
authors.forename: G Prem Veer
authors.initials: GP
authors.lastname: Reddy
authors.forename: Evelyn R
authors.initials: ER
authors.lastname: Barrack
mesh_terms: D015153:Blotting, Western; D045744:Cell Line, Tumor; D020022:Genetic Predisposition to Disease; D005973:Glutamine / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D008297:Male; D018895:Microsatellite Repeats / Q000235:genetics* / Q000502:physiology; D009376:Neoplasms, Hormone-Dependent / Q000235:genetics / Q000378:metabolism; D010957:Plasmids; D011110:Polymorphism, Genetic; D017430:Prostate-Specific Antigen / Q000235:genetics / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000378:metabolism; D011944:Receptors, Androgen / Q000235:genetics* / Q000378:metabolism; D014162:Transfection
chemical_list: D011944:Receptors, Androgen; D005973:Glutamine; D008156:Luciferases; D017430:Prostate-Specific Antigen