Abstract

Non-steroidal anti-inflammatory drugs (NSAIDs) are used for the treatment of inflammatory diseases. Recently, NSAIDs have been reported to have a chemopreventive effect 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. Treatment of human colon cancer cells as well as breast and lung cancer cells causes the up-regulation of novel gene (name as NAG-1) which we have characterized as member of the TGF-Bata superfamily gene. The project will be performed with three main aims; 1) to further characterize the expression of NAG-1 by NSAIDs and to explore the potential down regulation by pro-inflammatory agents, 2) to investigate the transacting elements in the NAG-1 gene promoter, 3) to identify of biological function(s) of NAG-1 protein in apoptosis and inflammation using cell culture and animal models. The study may provide new insights and mechanisms for the attenuation of colon cancer and anti-inflammatory activity of NSAIDs.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Intramural Research (Z01)
Project #
1Z01ES010016-02
Application #
6432216
Study Section
(LMC)
Project Start
Project End
Budget Start
Budget End
Support Year
2
Fiscal Year
2000
Total Cost
Indirect Cost

  Institution

Name
U.S. National Inst of Environ Hlth Scis
Department
Type
DUNS #
City
State
Country
United States
Zip Code

  Publications

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
Ge, C; Zhao, G; Li, Y et al. (2016) Role of Runx2 phosphorylation in prostate cancer and association with metastatic disease. Oncogene 35:366-76
Min, K-W; Liggett, J L; Silva, G et al. (2016) NAG-1/GDF15 accumulates in the nucleus and modulates transcriptional regulation of the Smad pathway. Oncogene 35:377-88
Wang, Xingya; Chrysovergis, Kali; Kosak, Justin et al. (2014) Lower NLRP3 inflammasome activity in NAG-1 transgenic mice is linked to a resistance to obesity and increased insulin sensitivity. Obesity (Silver Spring) 22:1256-63
Chrysovergis, K; Wang, X; Kosak, J et al. (2014) NAG-1/GDF-15 prevents obesity by increasing thermogenesis, lipolysis and oxidative metabolism. Int J Obes (Lond) 38:1555-64
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
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
Kambe, Atsushi; Yoshioka, Hiroki; Kamitani, Hideki et al. (2009) The cyclooxygenase inhibitor sulindac sulfide inhibits EP4 expression and suppresses the growth of glioblastoma cells. Cancer Prev Res (Phila) 2:1088-99
Moon, Yuseok; Kim, Jeung Il; Yang, Hyun et al. (2008) Growth compensatory role of sulindac sulfide-induced thrombospondin-1 linked with ERK1/2 and RhoA GTPase signaling pathways. Life Sci 82:591-9

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