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
Intramural Research (Z01)
Project #
1Z01ES010016-09
Application #
7593854
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
9
Fiscal Year
2007
Total Cost
$1,433,826
Indirect Cost

  Institution

Name
National Institute of Environmental Health Sciences
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) hNAG-1 increases lifespan by regulating energy metabolism and insulin/IGF-1/mTOR signaling. Aging (Albany NY) 6:690-704
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
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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