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NDRG2 Controls COX-2/PGE(2)-Mediated Breast Cancer Cell Migration and Invasion

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 o...

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Autores principales: Kim, Myung-Jin, Kim, Hak-Su, Lee, Soo-Hwan, Yang, Young, Lee, Myeong-Sok, Lim, Jong-Seok
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Korean Society for Molecular and Cellular Biology 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4213768/
https://www.ncbi.nlm.nih.gov/pubmed/25256221
http://dx.doi.org/10.14348/molcells.2014.0232
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author Kim, Myung-Jin
Kim, Hak-Su
Lee, Soo-Hwan
Yang, Young
Lee, Myeong-Sok
Lim, Jong-Seok
author_facet Kim, Myung-Jin
Kim, Hak-Su
Lee, Soo-Hwan
Yang, Young
Lee, Myeong-Sok
Lim, Jong-Seok
author_sort Kim, Myung-Jin
collection PubMed
description 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 E(2) (PGE(2)) 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.
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spelling pubmed-42137682014-10-30 NDRG2 Controls COX-2/PGE(2)-Mediated Breast Cancer Cell Migration and Invasion Kim, Myung-Jin Kim, Hak-Su Lee, Soo-Hwan Yang, Young Lee, Myeong-Sok Lim, Jong-Seok Mol Cells Article 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 E(2) (PGE(2)) 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. Korean Society for Molecular and Cellular Biology 2014-10-31 2014-09-26 /pmc/articles/PMC4213768/ /pubmed/25256221 http://dx.doi.org/10.14348/molcells.2014.0232 Text en The Korean Society for Molecular and Cellular Biology. All rights reserved. This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/3.0/
spellingShingle Article
Kim, Myung-Jin
Kim, Hak-Su
Lee, Soo-Hwan
Yang, Young
Lee, Myeong-Sok
Lim, Jong-Seok
NDRG2 Controls COX-2/PGE(2)-Mediated Breast Cancer Cell Migration and Invasion
title NDRG2 Controls COX-2/PGE(2)-Mediated Breast Cancer Cell Migration and Invasion
title_full NDRG2 Controls COX-2/PGE(2)-Mediated Breast Cancer Cell Migration and Invasion
title_fullStr NDRG2 Controls COX-2/PGE(2)-Mediated Breast Cancer Cell Migration and Invasion
title_full_unstemmed NDRG2 Controls COX-2/PGE(2)-Mediated Breast Cancer Cell Migration and Invasion
title_short NDRG2 Controls COX-2/PGE(2)-Mediated Breast Cancer Cell Migration and Invasion
title_sort ndrg2 controls cox-2/pge(2)-mediated breast cancer cell migration and invasion
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4213768/
https://www.ncbi.nlm.nih.gov/pubmed/25256221
http://dx.doi.org/10.14348/molcells.2014.0232
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