Accession Number : ADA621296


Title :   Androgenic Regulation of White Adipose Tissue-Prostate Cancer Interactions


Descriptive Note : Final rept. 1 May 2010-31 May 2015


Corporate Author : M D ANDERSON CANCER CENTER HOUSTON TX


Personal Author(s) : Thompson, Timothy C


Full Text : https://apps.dtic.mil/dtic/tr/fulltext/u2/a621296.pdf


Report Date : Aug 2015


Pagination or Media Count : 24


Abstract : Glipr1 (mouse)/GLIPR1 (human) is a direct p53 target gene that encodes a member of the pathogenesis-related protein family. This 28-kDa protein has a putative signal peptide sequence and a transmembrane domain suggesting extracellular functional activity. We have shown that Glipr1/GLIPR1 functions as a tumor suppressor through proapoptotic signaling in prostate cancer and potentially other malignancies. We recently discovered that recombinant Glipr1/GLIPR1 protein (rGlipr1/rGLIPR1) treatment results in growth arrest/apoptotic cell death in multiple prostate cancer cell lines in vitro. Further preclinical studies using PC-3 xenograft models demonstrated that rGLIPR1 suppressed PC-3 tumor growth when administered intratumorally or intraperitoneally. Although the direct growth suppressor/pro-apoptotic activities of Glipr1/GLIPR1 are now established, the physiological functions of GLIPR1 remain largely unknown. To further study Glipr1/GLIPR1 protein functions we generated mice harboring a targeted inactivation of the Glipr1 gene. We discovered that the wet weight of Glipr1 KO male white adipose tissue (WAT) was increased compare to the Glipr+/+ male littermates (Glipr1 WT). Based on these initial observations we pursued additional experiments. Overall, our preliminary data indicate that, in addition to direct growth suppressor/pro-apoptotic activities of Glipr1/GLIPR1 in prostate cancer cells, testosterone stimulated, prostate derived serum Glipr1/GLIPR1 is a hormone that can inhibit WAT function, including suppression of leptin secretion. Increased serum leptin levels may promote prostate cancer progression. We propose to study gene expression in the WAT and prostate tissues of Glipr1 WT and Glipr1 KO animals to characterize the genetic pathways that are affected by the presence or absence of Glipr1.


Descriptors :   *ADIPOSE TISSUE , *GENE EXPRESSION , *PROSTATE CANCER , *PROTEINS , ANDROGENS , APOPTOSIS , BLOOD SERUM , CELLS(BIOLOGY) , GENES , INTERACTIONS , MACROPHAGES , MICE , PEPTIDES , RECEPTOR SITES(PHYSIOLOGY)


Subject Categories : Biochemistry
      Genetic Engineering and Molecular Biology
      Anatomy and Physiology
      Medicine and Medical Research


Distribution Statement : APPROVED FOR PUBLIC RELEASE