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.

National Institute of Health (NIH)
National Institute of Environmental Health Sciences (NIEHS)
Intramural Research (Z01)
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Binder, April K; Kosak, Justin P; Janardhan, Kyathanahalli S et al. (2016) Expression of Human NSAID Activated Gene 1 in Mice Leads to Altered Mammary Gland Differentiation and Impaired Lactation. PLoS One 11:e0146518
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Wang, Xingya; Chrysovergis, Kali; Kosak, Justin et al. (2014) hNAG-1 increases lifespan by regulating energy metabolism and insulin/IGF-1/mTOR signaling. Aging (Albany NY) 6:690-704
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