title: NDRG2 controls COX-2/PGE₂-mediated breast cancer cell migration and invasion.
abstract: N-myc downstream-regulated gene 2 (NDRG2), which is known to have tumor suppressor functions, is frequently down-regulated in breast cancers and potentially involved in preventing the migration and invasion of malignant tumor cells. In the present study, we examined the inhibitory effects of NDRG2 overexpression, specifically focusing on the role of cyclooxygenase-2 (COX-2) in the migration of breast cancer cells. NDRG2 overexpression in MDA-MB-231 cells inhibited the expression of the COX-2 mRNA and protein, the transcriptional activity of COX-2, and prostaglandin E2 (PGE2) production, which were induced by a treatment with phorbol-12-myristate-13-acetate (PMA). Nuclear transcription factor-κB (NF-κB) signaling attenuated by NDRG2 expression resulted in a decrease in PMA-induced COX-2 expression. Interestingly, the inhibition of COX-2 strongly suppressed PMA-stimulated migration and invasion in MDA-MB-231-NDRG2 cells. Moreover, siRNA-mediated knockdown of NDRG2 in MCF7 cells increased the COX-2 mRNA and protein expression levels and the PMA-induced COX-2 expression levels. Consistent with these results, the migration and invasion of MCF7 cells treated with NDRG2 siRNA were significantly enhanced following treatment with PMA. Taken together, our data show that the inhibition of NF-κB signaling by NDRG2 expression is able to suppress cell migration and invasion through the down-regulation of COX-2 expression.
authors.affiliation: Department of Biological Science and the Research Center for Women's Disease, Sookmyung Women's University, Seoul 140-742, Korea.
authors.forename: Myung-Jin
authors.initials: MJ
authors.lastname: Kim
authors.affiliation: Department of Biological Science and the Research Center for Women's Disease, Sookmyung Women's University, Seoul 140-742, Korea.
authors.forename: Hak-Su
authors.initials: HS
authors.lastname: Kim
authors.forename: Soo-Hwan
authors.initials: SH
authors.lastname: Lee
authors.affiliation: Department of Biological Science and the Research Center for Women's Disease, Sookmyung Women's University, Seoul 140-742, Korea.
authors.forename: Young
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Biological Science and the Research Center for Women's Disease, Sookmyung Women's University, Seoul 140-742, Korea.
authors.forename: Myeong-Sok
authors.initials: MS
authors.lastname: Lee
authors.affiliation: Department of Biological Science and the Research Center for Women's Disease, Sookmyung Women's University, Seoul 140-742, Korea.
authors.forename: Jong-Seok
authors.initials: JS
authors.lastname: Lim
mesh_terms: D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology*; D002465:Cell Movement / Q000235:genetics; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism*; D015232:Dinoprostone / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D006801:Humans; D061986:MCF-7 Cells; D016328:NF-kappa B / Q000378:metabolism; D009361:Neoplasm Invasiveness; D034741:RNA, Small Interfering / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics; D019076:Transgenes / Q000235:genetics; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: C466228:NDRG2 protein, human; D016328:NF-kappa B; D034741:RNA, Small Interfering; D025521:Tumor Suppressor Proteins; D051546:Cyclooxygenase 2; D015232:Dinoprostone
keywords: COX-2; NDRG2; NF-κB; breast cancer; invasion; migration