down-regulation of ndrg1 promotes migration of cancer cells during reoxygenation下调的复氧期间ndrg1促进癌细胞的迁移.pdfVIP

Down-Regulation of NDRG1 Promotes Migration of Cancer Cells during Reoxygenation 1 1 1 2 3 4 Liang-Chuan Lai , Yi-Yu Su , Kuo-Chih Chen , Mong-Hsun Tsai , Yuh-Pyng Sher , Tzu-Pin Lu , Chien- 4 4 Yueh Lee , Eric Y. Chuang * 1 Graduate Institute of Physiology, National Taiwan University, Taipei, Taiwan, 2 Institute of Biotechnology, National Taiwan University, Taipei, Taiwan, 3 Graduate Institute of Clinical Medical Science, China Medical University, Taichung, Taiwan, 4 Graduate Institute of Biomedical Electronics and Bioinformatics, National Taiwan University, Taipei, Taiwan Abstract 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 enrich