Accession Number : ADA444681


Title :   Selenoproteins and Prostate Cancer


Descriptive Note : Annual summary rept. 15 Oct 2004-14 Oct 2005


Corporate Author : ILLINOIS UNIV AT CHICAGO


Personal Author(s) : Navsariwala, Veda


Full Text : http://www.dtic.mil/dtic/tr/fulltext/u2/a444681.pdf


Report Date : Nov 2005


Pagination or Media Count : 10


Abstract : For this postdoctoral fellowship the specific role of selenoproteins in prostate carcinogenesis is being investigated using a cell culture model system. First, the biological consequence of varying allelic identities in the selenoprotein glutathione peroxidase (GPx-1) in response to selenium (Se) supplementation was determined. GPx-1 has either a leucine (leu) or proline (pro) amino acid at the 198 codon, and cancer risk has been shown to vary depending on the allelic identity. Our investigation showed that the prostate cell line LNCaP containing the amino acid leu at the 198 codon was more responsive to Se supplementation although its baseline GPx activity was lower compared to cells with a pro at the same codon. These studies have increased our understanding of the effect of genetic variations in GPx-1 on the response to dietary Se and would be relevant to the findings from the SELECT trial on the observed effects of Se supplementation. The second objective was to investigate the effect of reduced levels of selenoproteins on DNA damage and cell proliferation. Significant progress has been made in reducing GPx-1 levels in prostate cell lines using the siRNA technique. Efforts are now in progress to investigate the biological consequence of these reduced levels. It is being investigated whether reduced GPx-1 levels increase DNA damage caused due to UVC treatment and whether this effect is attenuated if Se is supplemented in the medium prior to UV treatment. Collectively, these studies will help determine whether selenium effects in prostate carcinogenesis are mediated through selenoproteins. Understanding the mechanism of action would help maximize benefits of Se as a chemopreventive agent.


Descriptors :   *PROTEINS , *SELENIUM , *PROSTATE CANCER , ULTRAVIOLET RADIATION , CELLS(BIOLOGY) , GENETICS , ONCOGENESIS , LEUCINE , AMINO ACIDS , PEROXIDASES , PROSTATE GLAND , GLUTATHIONE


Subject Categories : Biochemistry
      Medicine and Medical Research


Distribution Statement : APPROVED FOR PUBLIC RELEASE