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.

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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
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
Sukhthankar, Mugdha; Yamaguchi, Kiyoshi; Lee, Seong-Ho et al. (2008) A green tea component suppresses posttranslational expression of basic fibroblast growth factor in colorectal cancer. Gastroenterology 134:1972-80
Kang, Hyo Jin; Kim, Hee Jeong; Kwon, Sang Hoon et al. (2008) BRCA1 modulates sensitivity to 5F-203 by regulating xenobiotic stress-inducible protein levels and EROD activity. Cancer Chemother Pharmacol 62:689-97
Kambe, Atsushi; Iguchi, Genzo; Moon, Yuseok et al. (2008) Regulation of EP4 expression via the Sp-1 transcription factor: inhibition of expression by anti-cancer agents. Biochim Biophys Acta 1783:1211-9
Zhu, Hong; Glasgow, Wayne; George, Margaret D et al. (2008) 15-lipoxygenase-1 activates tumor suppressor p53 independent of enzymatic activity. Int J Cancer 123:2741-9
Yoshioka, Hiroki; Kamitani, Hideki; Watanabe, Takashi et al. (2008) Nonsteroidal anti-inflammatory drug-activated gene (NAG-1/GDF15) expression is increased by the histone deacetylase inhibitor trichostatin A. J Biol Chem 283:33129-37
Shim, Minsub; Eling, Thomas E (2008) Vitamin E succinate induces NAG-1 expression in a p38 kinase-dependent mechanism. Mol Cancer Ther 7:961-71
Taniura, Seijiro; Kamitani, Hideki; Watanabe, Takashi et al. (2008) Induction of cyclooxygenase-2 expression by interleukin-1beta in human glioma cell line, U87MG. Neurol Med Chir (Tokyo) 48:500-5;discussion 505