Bone morphogenetic protein-4 induced by NDRG2 expression inhibits MMP-9 activity in breast cancer cells

Biochem Biophys Res Commun. 2009 Jul 24;385(2):198-203. doi: 10.1016/j.bbrc.2009.05.038. Epub 2009 May 19.


In the current study, we examined the function of N-myc downstream-regulated gene 2 (NDRG2) expression in breast cancer cells, especially focusing on the role of bone morphogenetic protein-4 (BMP-4) induced by NDRG2. NDRG2 expression in MDA-MB-231 cells inhibited the mRNA expression of several matrix metalloproteinases (MMPs) and the gelatinolytic activity of MMP-9. Interestingly, a specific induction of active BMP-4 was exclusively observed in MDA-MB-231-NDRG2 cells but not in MDA-MB-231-mock cells. Neutralization of BMP-4 in MDA-MB-231-NDRG2 cells resulted in the rescue of MMP-9 mRNA expression and migration capacity. In addition, treatment with recombinant BMP-4 dramatically suppressed MMP-9 mRNA expression, gelatinolytic MMP-9 activity, migration, and invasion capacity both in MDA-MB-231 and PMA-treated MCF-7 cells. Collectively, our data show that BMP-4 induced by NDRG2 expression inhibits the metastatic potential of breast cancer cells, especially via suppression of MMP-9 activity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bone Morphogenetic Protein 4 / metabolism*
  • Bone Morphogenetic Protein 4 / pharmacology
  • Breast Neoplasms / enzymology
  • Breast Neoplasms / pathology*
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Female
  • Humans
  • Matrix Metalloproteinase 9 / genetics
  • Matrix Metalloproteinase Inhibitors*
  • Neoplasm Invasiveness
  • Neoplasm Metastasis
  • RNA, Messenger / biosynthesis
  • Recombinant Proteins / pharmacology
  • Tumor Suppressor Proteins / biosynthesis*


  • BMP4 protein, human
  • Bone Morphogenetic Protein 4
  • Matrix Metalloproteinase Inhibitors
  • NDRG2 protein, human
  • RNA, Messenger
  • Recombinant Proteins
  • Tumor Suppressor Proteins
  • Matrix Metalloproteinase 9