Accession Number : ADA612331


Title :   AR Alternative Splicing and Prostate Cancer Progression


Descriptive Note : Final rept. 1 Jul 2010-30 Jun 2013


Corporate Author : MINNESOTA UNIV MINNEAPOLIS


Personal Author(s) : Dehm, Scott M


Full Text : http://www.dtic.mil/dtic/tr/fulltext/u2/a612331.pdf


Report Date : Jul 2013


Pagination or Media Count : 55


Abstract : Androgen depletion therapy for advanced prostate cancer (PCa) invariably fails, and PCa recurs with an aggressive and lethal castration-resistant (CR) phenotype. Although androgen depletion inhibits activity of the androgen receptor (AR), continued AR function is important for resistance to androgen depletion. Therefore, even though this stage of the disease is often referred to as androgen-independent (AI), CRPCa remains an AR-dependent disease. Recently, alternatively-spliced, COOH-terminally truncated AR isoform variants have been identified in CRPCa cells and clinical tissues. These isoform variants function as constitutively active AR transcription factors that can support the CRPCa phenotype in model systems. The purpose of this project is to understand the mechanisms underlying increased expression and activity of these truncated AR isoform variants in CRPCa. Our work provides the first evidence that structural alterations in the AR gene may underlie disrupted AR splicing patterns at this stage of the disease. This knowledge could lead to better treatments or management of patients with CRPCa.


Descriptors :   *ANDROGENS , *PROSTATE CANCER , CELLS(BIOLOGY) , RECEPTOR SITES(PHYSIOLOGY)


Subject Categories : Biochemistry
      Medicine and Medical Research


Distribution Statement : APPROVED FOR PUBLIC RELEASE