In Vivo Knockdown of the Androgen Receptor Results in Regression and Growth Inhibition of Androgen-i

• 作 者: PaulS.Rennie;RobertSnoek;HelenCheng;KatiaMargiotti;LatifA.Wafa;ColleenC.Nelson;MartinE.Gleave;
• 机 构: The Prostate Centre at Vancouver General Hospital Department of Urologic Sciences University of Brit
• 出 处: BIT Life Sciences' 1st Annual World Cancer Congess-2008(
• 发表日期: 2008年期

　　Progression to the castration resistant, androgen independent state is the incurable and lethal end stage of prostate cancer, where the tumors are no longer dependent on circulating androgens for growth.However, there is strong evidence that the androgen receptor (AR), the protein that mediates androgen actions, still plays a central role in this process.In a previous report (Cheng et al., Cancer Res, 2006), we used an antibiotic (doxycyeline)-inducible short hairpin RNA (shRNA) to knockdown the AR in androgen-dependent LNCaP prostate cancer tumor xenografts in immunocompromised mice and found that we could decrease serum PSA to well below castration nadir levels and could significantly retard tumor growth over the entire 55-day experimental period, with no evidence of progression to androgen independence.This was the first demonstration that in vivo knockdown of AR could delay or prevent progression to androgen independence.In the present study, we tested whether knockdown of the AR in an androgen-independent human prostate cancer (C4-2 cells) could affect PSA secretion and tumor growth.Changes in serum PSA levels and tumor volumes after induction ofAR shRNA fell into two subgroups based on their responses.