NSAID Activated Gene (NAG-1), a Modulator of Tumorigenesis

Thomas E. Eling^1,*, Seung Joon Baek², Minsub Shim¹ and Chang Ho Lee³  

¹National Institute of Environmental Health Sciences, National Institute of Health, Research Triangle Park, NC 27709, USA ²Department of Pathobiology, College of Veterinary Medicine, University of Tennessee, Knoxville, TN 37996, USA ³Department of Biology, Kangnung National University, 210-702, Korea  

The NSAID activated gene (NAG-1), a member of the TGF-β superfamily, is involved in tumor progression and development. The over-expression of NAG-1 in cancer cells results in growth arrest and increase in apoptosis, suggesting that NAG-1 has anti-tumorigenic activity. This conclusion is further supported by results of experiments with transgenic mice that ubiquitously express human NAG-1. These transgenic mice are resistant to the development of intestinal tumors following treatment with azoxymethane or by introduction of a mutant APC gene. In contrast, other data suggest a pro-tumorigenic role for NAG-1, for example, high expression of NAG-1 is frequently observed in tumors. NAG-1 may be like other members of the TGF-β superfamily, acting as a tumor suppressor in the early stages, but acting pro-tumorigenic at the later stages of tumor progression. The expression of NAG-1 can be increased by treatment with drugs and chemicals documented to prevent tumor formation and development. Most notable is the increase in NAG-1 expression by the inhibitors of cyclooxygenases that prevent human colorectal cancer development. The regulation of NAG-1 is complex, but these agents act through either p53 or EGR-1 related pathways. In addition, an increase in NAG-1 is observed in inhibition of the AKT/GSK-3β pathway, suggesting NAG-1 alters cell survival. Thus, NAG-1 expression is regulated by tumor suppressor pathways and appears to modulate tumor progression.
 

Anti-tumorigenic, Cancer, Cox inhibitor, Minmice, NAG-1, Tumor suppressor