Abstract

Non-steroidal anti-inflammatory drugs (NSAIDs) are used for the treatment of inflammatory diseases. Recently, NSAIDs have been reported to have chemopreventive effects on the development of human colorectal cancer. NSAIDs can inhibit COX-1 and/or COX-2 activity and thus inhibit prostaglandin synthesis. However, some reports indicate that the chemopreventive effect on colon cancer may, in part, be independent of prostaglandin inhibition could dependent on gene expression. Our goal is to identify and characterize genes that are regulated by Cox inhibitors including selective Cox inhibitors. Treatment of human cancer cells with NSAIDs caused the up-regulation of novel gene NAG-1, or NSAIDs activated gene that is member of the TGF-b superfamily gene. The project has with three aims;1) to further characterize the expression of NAG-1 by NSAIDs and other drugs,2) to investigate the transacting elements in the NAG-1 gene promoter responsible for the regulation, and 3) to identify of biological function(s) of NAG-1 as related to cancer and inflammation.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Investigator-Initiated Intramural Research Projects (ZIA)
Project #
1ZIAES010016-15
Application #
8734044
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
15
Fiscal Year
2013
Total Cost
$972,039
Indirect Cost

  Institution

Name
National Institute of Environmental Health Sciences
Department
Type
DUNS #
City
State
Country
Zip Code

  Publications

Shimizu, Sachie; Kadowaki, Mitsutoshi; Yoshioka, Hiroki et al. (2013) Proteasome inhibitor MG132 induces NAG-1/GDF15 expression through the p38 MAPK pathway in glioblastoma cells. Biochem Biophys Res Commun 430:1277-82
Kim, J M; Kosak, J P; Kim, J K et al. (2013) NAG-1/GDF15 transgenic mouse has less white adipose tissue and a reduced inflammatory response. Mediators Inflamm 2013:641851
Wang, Xingya; Baek, Seung Joon; Eling, Thomas E (2013) The diverse roles of nonsteroidal anti-inflammatory drug activated gene (NAG-1/GDF15) in cancer. Biochem Pharmacol 85:597-606
Kadowaki, Mitsutoshi; Yoshioka, Hiroki; Kamitani, Hideki et al. (2012) DNA methylation-mediated silencing of nonsteroidal anti-inflammatory drug-activated gene (NAG-1/GDF15) in glioma cell lines. Int J Cancer 130:267-77
Wang, Xingya; Chrysovergis, Kali; Bienstock, Rachelle J et al. (2012) The H6D variant of NAG-1/GDF15 inhibits prostate xenograft growth in vivo. Prostate 72:677-89
Whitlock, Nichelle C; Bahn, Jae Hoon; Lee, Seong-Ho et al. (2011) Resveratrol-induced apoptosis is mediated by early growth response-1, Kruppel-like factor 4, and activating transcription factor 3. Cancer Prev Res (Phila) 4:116-27
Wang, Xingya; Baek, Seung Joon; Eling, Thomas (2011) COX inhibitors directly alter gene expression: role in cancer prevention? Cancer Metastasis Rev 30:641-57
Wang, Xingya; Kingsley, Philip J; Marnett, Larry J et al. (2011) The role of NAG-1/GDF15 in the inhibition of intestinal polyps in APC/Min mice by sulindac. Cancer Prev Res (Phila) 4:150-60
Shim, Minsub; Foley, Julie; Anna, Colleen et al. (2010) Embryonic expression of cyclooxygenase-2 causes malformations in axial skeleton. J Biol Chem 285:16206-17
Ashwell, Melissa S; Ceddia, Ryan P; House, Ralph L et al. (2010) Trans-10, cis-12-conjugated linoleic acid alters hepatic gene expression in a polygenic obese line of mice displaying hepatic lipidosis. J Nutr Biochem 21:848-55

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