Down-Regulation of NDRG1 Promotes Migration of Cancer Cells during Reoxygenation 英文参考文献.docVIP

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Down-Regulation of NDRG1 Promotes Migration of Cancer Cells during Reoxygenation 英文参考文献.doc

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Down-Regulation of NDRG1 Promotes Migration of Cancer Cells during Reoxygenation 英文参考文献

Down-RegulationofNDRG1PromotesMigrationof CancerCellsduringReoxygenation Liang-ChuanLai1,Yi-YuSu1,Kuo-ChihChen1,Mong-HsunTsai2,Yuh-PyngSher3,Tzu-PinLu4 ,Chien- YuehLee4,EricY.Chuang4* 1GraduateInstituteofPhysiology,NationalTaiwanUniversity,Taipei,Taiwan,2InstituteofBiotechnology,NationalTaiwanUniversity,Taipei,Taiwan,3GraduateInstitute of Clinical Medical Science, China Medical University, Taichung, Taiwan, 4Graduate Institute of Biomedical Electronics and Bioinformatics, National Taiwan University, Taipei,Taiwan Abstract Onecharacteristicoftumormicroenvironmentisoxygenfluctuation,whichresultsfromhyper-proliferationandabnormal metabolismoftumorcellsaswellasdisorganizedneo-vasculature.Reoxygenationoftumorscaninduceoxidativestress, whichleadstoDNAdamageandgenomicinstability.Althoughthecellularresponsestohypoxiaarewellknown,littleis 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 24h followed by 24h of reoxygenationinnormoxia.Cellswereharvestedat0,1,4,8,12,and24hduringreoxygenation.Thetranscriptionalprofile ofMCF-7cellsuponreoxygenationwasexaminedusingIlluminaHuman-6v3BeadChips.Weidentified127differentially expressed genes, of which 53.1% were up-regulated and 46.9% were down-regulated upon reoxygenation. Pathway analysisrevealedthattheHIF-1-alphatranscriptionfactornetworkandvalidatedtargetsofC-MYCtranscriptionalactivation 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.TodeterminewhetherNDRG1playsaroleinreoxygenation,NDRG1proteinwasoverexpressedinMCF-7cells. Upon reoxygenation, overexpression of NDRG1