암세포에서 NAG-1의 발현 및 기능

Abstract

Nonsteroidal anti-inflammatory drug (NSAID)-activated gene-1 (NAG-1) was identified from indomethacin (a cyclooxygenase (COX) inhibitor)-induced gene library. NAG-1 is a member of TGF-β superfamily and is also known as macrophage inhibitory cytokine-1 (MIC-1), placental transforming growth factor β (PTGF-β), or prostate derived factor (PDF). Purified recombinant NAG-1 is able to inhibit lipopolysaccharide-induced TNF-α production in macrophages, suggesting that NAG-1 acts as an autocrine regulatory molecule. In vitro and in vivo NAG-1 has anti-tumorigenic and pro-apoptotic activities independent of COX inhibition. Not only NSAIDs but also several anti-tumorigenic compounds with chemopreventive activities, including resveratrol, genistein, catechins, and peroxisome proliferatorsactivated receptor-γ ligands, regulate NAG-1 expression in a prostaglandin-independent manner. Thus, pro-apoptotic activity of NAG-1 may provide a molecular basis to explain chemopreventive agentsmediated anti-tumorigenesis. However, the biological activity of NAG-1 is very poorly characterized, and reports in the literature show high expression in tumors. Thus, understanding the regulatory mechanism of NAG-1 by chemotherapeutic and chemopreventive agents and their implications in cancer treatments may provide a rational approach for using such as tumor therapeutic target. In this study, we summarize biological role of NAG-1 and discuss the potential molecular basis for their expressional regulation.