Nonsteroidal antiinflammatory drugs (NSAlDs) have been used for the treatment of inflammatory disease. NSAlDs also have anti-tumorigenic activity. An anti-tumorigenic protein, called NSAID activated gene-1 (NAG-1), mediates one molecular mechanism for NSAID-induced anti-tumorigenic activity. It is possible that NAG-1 may contribute to anti-tumorigenic and anti-inflammatory activity produced by NSAlDs. Therefore, the elucidation of transcriptional regulation and the biological functions provides a novel mechanism to better understand cancer and inflammation. The research objectives are to study how NSAlDs regulate NAG-1 gene expression, and also how environmental factors may affect-NAG-1 gene regulation to prevent cancer and inflammation.
Two specific aims are involved in this research. First, the promoter of NAG-1 gene will be used to elucidate its NSAID responsiveness and then cloning the NSAID responsive binding protein. Secondly, the biological function of NAG-1 will be assessed using purified recombinant NAG-1 protein and NAG-1 overexpressing transgenic mice, to elucidate its anti-tumorigenic and anti-inflammatory activities. This proposal also seeks to address how NSAlDs regulate anti-tumorigenesis, and whether other factors, believed to modulate tumor development, could do so by altering gene regulation. This study may also provide new insights into how chemical and environmental factors influence cancer development and lead to the development of novel family anti-tumorigenic compounds, which are not cyclooxygenase (COX) inhibitors. Cancer and inflammation are certainly environmentally relevant problems and thus this project will provide new clues to aid in the understanding of how these drugs alter tumor development.

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Career Transition Award (K22)
Project #
1K22ES011657-01A1
Application #
6610681
Study Section
Special Emphasis Panel (ZES1-JAB-D (TP))
Program Officer
Shreffler, Carol K
Project Start
2003-09-08
Project End
2006-06-30
Budget Start
2003-09-08
Budget End
2004-06-30
Support Year
1
Fiscal Year
2003
Total Cost
$108,000
Indirect Cost
Name
University of Tennessee Knoxville
Department
Pathology
Type
Schools of Veterinary Medicine
DUNS #
003387891
City
Knoxville
State
TN
Country
United States
Zip Code
37996
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