Bone morphogenetic protein-4 induced by NDRG2 expression inhibits MMP-9 activity in breast cancer cells.
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.
Shon
Soo-Kyung
SK
Department of Biological Science and The Research Center for Women's Diseases, Sookmyung Women's University, Seoul, Republic of Korea.
Kim
Aeyung
A
Kim
Ji Young
JY
Kim
Keun Il
KI
Yang
Young
Y
Lim
Jong-Seok
JS
D055415:Bone Morphogenetic Protein 4 / Q000378:metabolism* / Q000494:pharmacology; D001943:Breast Neoplasms / Q000201:enzymology / Q000473:pathology*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D005260:Female; D006801:Humans; D020780:Matrix Metalloproteinase 9 / Q000235:genetics; D061965:Matrix Metalloproteinase Inhibitors; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D012333:RNA, Messenger / Q000096:biosynthesis; D011994:Recombinant Proteins / Q000494:pharmacology; D025521:Tumor Suppressor Proteins / Q000096:biosynthesis*
C525809:BMP4 protein, human; D055415:Bone Morphogenetic Protein 4; D061965:Matrix Metalloproteinase Inhibitors; C466228:NDRG2 protein, human; D012333:RNA, Messenger; D011994:Recombinant Proteins; D025521:Tumor Suppressor Proteins; D020780:Matrix Metalloproteinase 9