Accession Number : ADA483723


Title :   Inhibition of Androgen-Independent Growth of Prostate Cancer by siRNA- Mediated Androgen Receptor Gene Silencing


Descriptive Note : Final rept. 15 Jan 2004-14 Jan 2008


Corporate Author : KANSAS UNIV MEDICAL CENTER KANSAS CITY


Personal Author(s) : Li, Benyi


Full Text : https://apps.dtic.mil/dtic/tr/fulltext/u2/a483723.pdf


Report Date : Feb 2008


Pagination or Media Count : 102


Abstract : To determine if AR gene silencing in prostate cancer cells via RNA interference mechanism leads to disruption of androgen-independent progression. We generated a recombinant AAV for long-term expression of a hairpin-structured AR siRNA in vivo. Then we determined the essential role of the androgen receptor in androgen-independent growth of prostate cancer. We demonstrated that knocking down AR expression abolished tumor growth and blocked androgen-independent transition in LNCaP and LAPC-4 cell-derived xenografts. In addition, we observed that AR silencing resulted in a significant decrease of androgen-independent tumor growth in C4-2 cell-derived xenografts in castrated mice. We also demonstrated that knocking down AR expression by systemic delivery of the AAV particle eradicated CWR22RV1 androgen-independent xenograft tumors but not AR-null PC-3 xenograft tumors. We analyzed the mechanisms for AR siRNA-induced cell death and identified the anti-apoptotic proteins SGK1 and Bcl-xL, as the downstream effecters of AR-mediated survival pathway. Most of these results were published (Appendix II-VI).


Descriptors :   *PROSTATE CANCER , *ANDROGENS , RECEPTOR SITES(PHYSIOLOGY) , APOPTOSIS , RIBONUCLEIC ACIDS , GENES , GROWTH(PHYSIOLOGY)


Subject Categories : Medicine and Medical Research


Distribution Statement : APPROVED FOR PUBLIC RELEASE