Accession Number : ADA570755


Title :   The Role of AR- and VDR-Modulated miRNAs in Sensitization of Prostate Cancer Cells to Therapy


Descriptive Note : Annual summary 30 Sep 2011-29 Sep 2012


Corporate Author : STATE UNIV OF NY AT RENSSELAER RESEARCH FOUDATION


Personal Author(s) : Wang, Wei-Lin W


Full Text : https://apps.dtic.mil/dtic/tr/fulltext/u2/a570755.pdf


Report Date : Oct 2012


Pagination or Media Count : 96


Abstract : Epidemiological evidence has demonstrated an inverse association between serum vitamin D levels and sunlight exposure to prostate cancer incidence. In addition, serum androgen levels and biologically available testosterone decrease significantly in elder men while the incidence rate of prostate cancer increases. These findings lead to the hypothesis that androgen- and vitamin D-mediated signaling events may act together to inhibit prostate tumor initiation and/or development. Using concurrent microarray analyses, we demonstrated that testosterone and 1,25(OH)2D3 co-operate to regulate mRNA and miRNA expression, including some well-defined oncogenes and tumor suppressor genes. Pheno typically, this results in G0/G1 cell cycle arrest and increased neutral lipid accumulation in LNCaP cells, as a consequence of repression of various cell cycle regulators and the up-regulation of PPAR alpha; respectively. This suggests that the cross talk between T and 1,25(OH)2D3 induces cell cycle arrest and promotes cell differentiation in LNCaP cells. It is important ton ote that co-treatment of LNCaP cells with testosterone, 1,25(OH)2D3 and other standard therapeutics, including bicalutamide, docetaxel and TRAIL did not affect the potencies of these treatments, though there were no synergistic effects either. This suggests that androgen andvitamin D supplementation slow disease progression without affecting the efficacy of standard therapies for prostate cancer. Further analysis is still required to elucidate the underlying mechanisms of T and 1,25(OH)2D3 to modulate key mRNA and miRNA and their significance in prostate tumorigenesis and therapeutic interventions.


Descriptors :   *PROSTATE CANCER , ANDROGENS , EPIDEMIOLOGY , GROWTH(PHYSIOLOGY) , NEOPLASMS , ONCOGENIC VIRUSES , REGULATORS , TESTOSTERONE , THERAPY , VITAMIN D


Subject Categories : Anatomy and Physiology
      Medicine and Medical Research


Distribution Statement : APPROVED FOR PUBLIC RELEASE