Regulation of N-Myc downstream regulated gene 2 by bile acids.

Abstract

Here we report that bile acid chenodeoxycholic acid (CDCA) and synthetic farnesoid X receptor (FXR) agonist GW4064 robustly induced tumor suppressor N-Myc downstream regulated gene 2 (NDRG2) expression in human hepatoma cells and primary hepatocytes. Knockdown of FXR abolished the induction by CDCA, whereas overexpression of a constitutively active form of FXR increased NDRG2 expression. A FXR-response element was identified within intronic regions of human and murine genes. Moreover, mice given GW4064 exhibit an increase of Ndrg2 expression in liver and kidney, where both NDRG2 and FXR are enriched. The identification of NDRG2 as a bile acid regulated gene may provide novel knowledge toward the understanding of NDRG2 physiological function and the link between metabolism and cancer.

• Authors: Cédric Langhi, Elena Pedraz-Cuesta, Yolanda Donate, Pedro F Marrero, Diego Haro, Joan C Rodríguez
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 434 Issue 1 Pg. 102-9 (Apr 26 2013) ISSN: 1090-2104 [Electronic] United States
• PMID: 23541942 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2013 Elsevier Inc. All rights reserved.

Chemical References

• Adaptor Proteins, Signal Transducing
• Bile Acids and Salts
• NDRG2 protein, human
• Ndr2 protein, mouse
• Proteins
• Receptors, Cytoplasmic and Nuclear
• Tumor Suppressor Proteins
• farnesoid X-activated receptor

Topics

• Adaptor Proteins, Signal Transducing
• Animals
• Bile Acids and Salts (pharmacology)
• Cell Line, Tumor
• Gene Expression Regulation, Neoplastic (drug effects)
• Gene Knockdown Techniques
• Hep G2 Cells
• Humans
• Male
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• Proteins (genetics, metabolism)
• Receptors, Cytoplasmic and Nuclear (agonists, antagonists & inhibitors, genetics)
• Tumor Suppressor Proteins (genetics, metabolism)
• Up-Regulation (physiology)