title: Androgen receptor signaling is required for androgen-sensitive human prostate cancer cell proliferation and survival.
abstract: BACKGROUND: Androgens and androgen receptors (AR) regulate normal prostate development and growth. They also are involved in pathological development of prostatic diseases, including benign prostatic hyperplasia (BPH) and prostate cancer (PCa). Antiandrogen therapy for PCa, in conjunction with chemical or surgical castration, offers initial positive responses and leads to massive prostate cell death. However, cancer cells later appear as androgen-independent PCa. To investigate the role of AR in prostate cell proliferation and survival, we introduced a vector-based small interfering RNA (siRNA). This siRNA targeted 5'-untranslated region of AR mRNA for extended suppression of AR expression in androgen-sensitive human prostate LNCaP cells. RESULTS: The siRNA design successfully suppressed endogenous AR expression, as revealed by western blotting and immunofluorescence staining in LNCaP cells. LNCaP cells did not proliferate in the absence of AR and underwent apoptosis, based on elevated phospho-Histone H2B expression and higher number of apoptotic body as compared to control cells. CONCLUSION: We demonstrated that AR is vital for prostate cell proliferation and survival in this androgen-sensitive prostate cell line. These results further strengthen the hypothesis that AR can be a therapeutic target for treating androgen-sensitive stages of PCa. Unlike antiandorgens, however, siRNA targeting AR provides a direct inactivation of AR function through the suppression of AR protein expression.
authors.affiliation: Department of Urology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA. hk-lin@ouhsc.edu.
authors.forename: Qing
authors.initials: Q
authors.lastname: Yang
authors.forename: Kar-Ming
authors.initials: KM
authors.lastname: Fung
authors.forename: Wanda V
authors.initials: WV
authors.lastname: Day
authors.forename: Bradley P
authors.initials: BP
authors.lastname: Kropp
authors.forename: Hsueh-Kung
authors.initials: HK
authors.lastname: Lin