Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2013 Mar 1;85(5):597-606.
doi: 10.1016/j.bcp.2012.11.025. Epub 2012 Dec 7.

The diverse roles of nonsteroidal anti-inflammatory drug activated gene (NAG-1/GDF15) in cancer

Xingya Wang  1 , Seung Joon Baek  2 , Thomas E Eling  3
Affiliations
Review

The diverse roles of nonsteroidal anti-inflammatory drug activated gene (NAG-1/GDF15) in cancer

Xingya Wang et al. Biochem Pharmacol. .

Abstract

Nonsteroidal anti-inflammatory drug (NSAID) activated gene-1, NAG-1, is a divergent member of the transforming growth factor-beta (TGF-β) superfamily that plays a complex but poorly understood role in several human diseases including cancer. NAG-1 expression is substantially increased during cancer development and progression especially in gastrointestinal, prostate, pancreatic, colorectal, breast, melanoma, and glioblastoma brain tumors. Aberrant increases in the serum levels of secreted NAG-1 correlate with poor prognosis and patient survival rates in some cancers. In contrast, the expression of NAG-1 is up-regulated by several tumor suppressor pathways including p53, GSK-3β, and EGR-1. NAG-1 expression is also induced by many drugs and dietary compounds which are documented to prevent the development and progression of cancer in mouse models. Studies with transgenic mice expressing human NAG-1 demonstrated that the expression of NAG-1 inhibits the development of intestinal tumors and prostate tumors in animal models. Laboratory and clinical evidence suggest that NAG-1, like other TGF-β family members, may have different or pleiotropic functions in the early and late stages of carcinogenesis. Upon understanding the molecular mechanism and function of NAG-1 during carcinogenesis, NAG-1 may serve as a potential biomarker for the diagnosis and prognosis of cancer and a therapeutic target for the inhibition and treatment of cancer development and progression.

PubMed Disclaimer

Figures

Figure 1
Figure 1. Dimeric formation of mature NAG-1 and different forms of NAG-1 in cells
The pro-NAG-1 was cleaved at RXXR site and then secreted out the cells as a dimer. NAG-1 pro-peptide is also secreted out of cells.
Figure 2
Figure 2. Transcriptional regulation of NAG-1 by NSAIDs and dietary compounds
NAG-1 promoter contains several cis-acting and trans-acting elements. Both Sp1 and EGR-1 transcription factors have been identified to regulate the basal transcription of NAG-1. Two p53 sites that located within the -133 bp promoter play a pivotal role in dietary compound-induced NAG-1 expression.
See this image and copyright information in PMC

References

    1. Baek SJ, Kim KS, Nixon JB, Wilson LC, Eling TE. Cyclooxygenase inhibitors regulate the expression of a TGF-beta superfamily member that has proapoptotic and antitumorigenic activities. Mol Pharmacol. 2001;59:901–8. - PubMed
    1. Bootcov MR, Bauskin AR, Valenzuela SM, Moore AG, Bansal M, He XY, et al. MIC-1, a novel macrophage inhibitory cytokine, is a divergent member of the TGF-beta superfamily. Proc Natl Acad Sci U S A. 1997;94:11514–9. - PMC - PubMed
    1. Li PX, Wong J, Ayed A, Ngo D, Brade AM, Arrowsmith C, et al. Placental transforming growth factor-beta is a downstream mediator of the growth arrest and apoptotic response of tumor cells to DNA damage and p53 overexpression. J Biol Chem. 2000;275:20127–35. - PubMed
    1. Paralkar VM, Vail AL, Grasser WA, Brown TA, Xu H, Vukicevic S, et al. Cloning and characterization of a novel member of the transforming growth factor-beta/bone morphogenetic protein family. J Biol Chem. 1998;273:13760–7. - PubMed
    1. Bottner M, Laaff M, Schechinger B, Rappold G, Unsicker K, Suter-Crazzolara C. Characterization of the rat, mouse, and human genes of growth/differentiation factor-15/macrophage inhibiting cytokine-1 (GDF-15/MIC-1) Gene. 1999;237:105–11. - PubMed

Publication types

MeSH terms

Substances