Down-regulation of NDRG1 promotes migration of cancer cells during reoxygenation.

One characteristic of tumor microenvironment is oxygen fluctuation, which results from hyper-proliferation and abnormal metabolism of tumor cells as well as disorganized neo-vasculature. Reoxygenation of tumors can induce oxidative stress, which leads to DNA damage and genomic instability. Although...

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Autores principales: Liang-Chuan Lai, Yi-Yu Su, Kuo-Chih Chen, Mong-Hsun Tsai, Yuh-Pyng Sher, Tzu-Pin Lu, Chien-Yueh Lee, Eric Y Chuang
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Publicado: Public Library of Science (PLoS) 2011
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Acceso en línea:https://doaj.org/article/5051598b334d409e998b0c9d7bce035c
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spelling oai:doaj.org-article:5051598b334d409e998b0c9d7bce035c2021-11-18T06:47:01ZDown-regulation of NDRG1 promotes migration of cancer cells during reoxygenation.1932-620310.1371/journal.pone.0024375https://doaj.org/article/5051598b334d409e998b0c9d7bce035c2011-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21912630/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203One characteristic of tumor microenvironment is oxygen fluctuation, which results from hyper-proliferation and abnormal metabolism of tumor cells as well as disorganized neo-vasculature. Reoxygenation of tumors can induce oxidative stress, which leads to DNA damage and genomic instability. Although the cellular responses to hypoxia are well known, little is known about the dynamic response upon reoxygenation. In order to investigate the transcriptional responses of tumor adaptation to reoxygenation, breast cancer MCF-7 cells were cultured under 0.5% oxygen for 24 h followed by 24 h of reoxygenation in normoxia. Cells were harvested at 0, 1, 4, 8, 12, and 24 h during reoxygenation. The transcriptional profile of MCF-7 cells upon reoxygenation was examined using Illumina Human-6 v3 BeadChips. We identified 127 differentially expressed genes, of which 53.1% were up-regulated and 46.9% were down-regulated upon reoxygenation. Pathway analysis revealed that the HIF-1-alpha transcription factor network and validated targets of C-MYC transcriptional activation were significantly enriched in these differentially expressed genes. Among these genes, a subset of interest genes was further validated by quantitative reverse-transcription PCR. In particular, human N-MYC down-regulated gene 1 (NDRG1) was highly suppressed upon reoxygenation. NDRG1 is associated with a variety of stress and cell growth-regulatory conditions. To determine whether NDRG1 plays a role in reoxygenation, NDRG1 protein was overexpressed in MCF-7 cells. Upon reoxygenation, overexpression of NDRG1 significantly inhibited cell migration. Our results revealed the dynamic nature of gene expression in MCF-7 cells upon reoxygenation and demonstrated that NDRG1 is involved in tumor adaptation to reoxygenation.Liang-Chuan LaiYi-Yu SuKuo-Chih ChenMong-Hsun TsaiYuh-Pyng SherTzu-Pin LuChien-Yueh LeeEric Y ChuangPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 6, Iss 8, p e24375 (2011)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Liang-Chuan Lai
Yi-Yu Su
Kuo-Chih Chen
Mong-Hsun Tsai
Yuh-Pyng Sher
Tzu-Pin Lu
Chien-Yueh Lee
Eric Y Chuang
Down-regulation of NDRG1 promotes migration of cancer cells during reoxygenation.
description One characteristic of tumor microenvironment is oxygen fluctuation, which results from hyper-proliferation and abnormal metabolism of tumor cells as well as disorganized neo-vasculature. Reoxygenation of tumors can induce oxidative stress, which leads to DNA damage and genomic instability. Although the cellular responses to hypoxia are well known, little is known about the dynamic response upon reoxygenation. In order to investigate the transcriptional responses of tumor adaptation to reoxygenation, breast cancer MCF-7 cells were cultured under 0.5% oxygen for 24 h followed by 24 h of reoxygenation in normoxia. Cells were harvested at 0, 1, 4, 8, 12, and 24 h during reoxygenation. The transcriptional profile of MCF-7 cells upon reoxygenation was examined using Illumina Human-6 v3 BeadChips. We identified 127 differentially expressed genes, of which 53.1% were up-regulated and 46.9% were down-regulated upon reoxygenation. Pathway analysis revealed that the HIF-1-alpha transcription factor network and validated targets of C-MYC transcriptional activation were significantly enriched in these differentially expressed genes. Among these genes, a subset of interest genes was further validated by quantitative reverse-transcription PCR. In particular, human N-MYC down-regulated gene 1 (NDRG1) was highly suppressed upon reoxygenation. NDRG1 is associated with a variety of stress and cell growth-regulatory conditions. To determine whether NDRG1 plays a role in reoxygenation, NDRG1 protein was overexpressed in MCF-7 cells. Upon reoxygenation, overexpression of NDRG1 significantly inhibited cell migration. Our results revealed the dynamic nature of gene expression in MCF-7 cells upon reoxygenation and demonstrated that NDRG1 is involved in tumor adaptation to reoxygenation.
format article
author Liang-Chuan Lai
Yi-Yu Su
Kuo-Chih Chen
Mong-Hsun Tsai
Yuh-Pyng Sher
Tzu-Pin Lu
Chien-Yueh Lee
Eric Y Chuang
author_facet Liang-Chuan Lai
Yi-Yu Su
Kuo-Chih Chen
Mong-Hsun Tsai
Yuh-Pyng Sher
Tzu-Pin Lu
Chien-Yueh Lee
Eric Y Chuang
author_sort Liang-Chuan Lai
title Down-regulation of NDRG1 promotes migration of cancer cells during reoxygenation.
title_short Down-regulation of NDRG1 promotes migration of cancer cells during reoxygenation.
title_full Down-regulation of NDRG1 promotes migration of cancer cells during reoxygenation.
title_fullStr Down-regulation of NDRG1 promotes migration of cancer cells during reoxygenation.
title_full_unstemmed Down-regulation of NDRG1 promotes migration of cancer cells during reoxygenation.
title_sort down-regulation of ndrg1 promotes migration of cancer cells during reoxygenation.
publisher Public Library of Science (PLoS)
publishDate 2011
url https://doaj.org/article/5051598b334d409e998b0c9d7bce035c
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