Knockout AR in Prostate

Prostate cancer progresses from androgen-dependent to androgen-independent state. The androgen receptor (AR) isexpressed throughout progression. We would like to understand the AR role in this progression. Using lox-Cre methodology,we have generated mice in which AR function is abolished in the entire animal (ARKO) or tissue specific manner. We willgenerate mice with ARKO in prostate only or in different stages to be used to study prostate cancer progresses. Our Aimsfollow. 1: Generate mice lacking functional AR in prostate epithelium. 2: Generate inducible ARKO mouse line to be used todetermine potential effect of androgen in absence of AR on prostate growth/maintenance. 3: Determine AR role in prostatecancer development/progression by crossing ARKO mice with TRAMP mice to examine AR role in TRAMP induced prostatecancer and permit determination of points in prostate cancer requiring AR function. 4: Determine AR role in tumorigenicity ofandrogen-dependent and androgen-independent ARKO prostate cancer cell lines. The effect of AR loss in these cells will beexamined for ability to generate/promote tumors in mice. This year we generated mice with ARKO in the prostate epitheliumand will be able to continue the other aims in the proposal in the coming years.