https://scholars.lib.ntu.edu.tw/handle/123456789/520990
標題: | Down-regulation of NDRG1 promotes migration of cancer cells during reoxygenation | 作者: | LIANG-CHUAN LAI Su, Y.-Y. Chen, K.-C. Tsai, M.-H. Sher, Y.-P. TZU-PIN LU Lee, C.-Y. MONG-HSUN TSAI ERIC YAO-YU CHUANG |
公開日期: | 2011 | 卷: | 6 | 期: | 8 | 來源出版物: | PLoS ONE | 摘要: | 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. ? 2011 Lai et al. |
URI: | https://www.scopus.com/inward/record.uri?eid=2-s2.0-80052298024&doi=10.1371%2fjournal.pone.0024375&partnerID=40&md5=b75483729eab624366aa21a96d38edde https://scholars.lib.ntu.edu.tw/handle/123456789/520990 |
ISSN: | 1932-6203 | DOI: | 10.1371/journal.pone.0024375 | SDG/關鍵字: | hypoxia inducible factor 1alpha; N MYC down regulated gene 1 protein; oncoprotein; oxygen; unclassified drug; cell cycle protein; microRNA; Myc protein; N myc downstream regulated gene 1 protein; N-myc downstream-regulated gene 1 protein; oxygen; signal peptide; transcription factor; article; breast cancer; cancer cell; cancer cell culture; cell growth; cell migration; cellular stress response; controlled study; down regulation; gene expression profiling; gene expression regulation; gene function; gene overexpression; gene repression; gene targeting; genetic association; growth regulation; human; human cell; N MYC down regulated gene 1; oncogene c myb; promoter region; reoxygenation; transcription initiation; tumor microenvironment; upregulation; biology; breast tumor; cell hypoxia; cell motion; DNA microarray; down regulation; female; genetics; metabolism; pathology; tumor cell line; Breast Neoplasms; Cell Cycle Proteins; Cell Hypoxia; Cell Line, Tumor; Cell Movement; Computational Biology; Down-Regulation; Female; Gene Expression Profiling; Humans; Intracellular Signaling Peptides and Proteins; MicroRNAs; Oligonucleotide Array Sequence Analysis; Oxygen; Proto-Oncogene Proteins c-myc; Transcription Factors |
顯示於: | 流行病學與預防醫學研究所 |
在 IR 系統中的文件,除了特別指名其著作權條款之外,均受到著作權保護,並且保留所有的權利。