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Identification of Y-box binding protein 1 as a core regulator of MEK/ERK pathway-dependent gene signatures in colorectal cancer cells
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نویسنده
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jürchott k. ,kuban r.-j. ,krech t. ,blüthgen n. ,stein u. ,walther w. ,friese c. ,kiełbasa s.m. ,ungethüm u. ,lund p. ,knösel t. ,kemmner w. ,morkel m. ,fritzmann j. ,schlag p.m. ,birchmeier w. ,krueger t. ,sperling s. ,sers c. ,royer h.-d. ,herzel h. ,schäfer r.
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منبع
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plos genetics - 2010 - دوره : 6 - شماره : 12 - صفحه:1 -19
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چکیده
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Transcriptional signatures are an indispensible source of correlative information on disease-related molecular alterations on a genome-wide level. numerous candidate genes involved in disease and in factors of predictive,as well as of prognostic,value have been deduced from such molecular portraits,e.g. in cancer. however,mechanistic insights into the regulatory principles governing global transcriptional changes are lagging behind extensive compilations of deregulated genes. to identify regulators of transcriptome alterations,we used an integrated approach combining transcriptional profiling of colorectal cancer cell lines treated with inhibitors targeting the receptor tyrosine kinase (rtk)/ras/mitogenactivated protein kinase pathway,computational prediction of regulatory elements in promoters of co-r egulated genes,chromatin-based and functional cellular assays. we identified commonly co-regulated,proliferation-associated target genes that respond to the mapk pathway. we recognized e2f and nfy transcription factor binding sites as prevalent motifs in those pathway-responsive genes and confirmed the predicted regulatory role of y-box binding protein 1 (ybx1) by reporter gene,gel shift,and chromatin immunoprecipitation assays. we also validated the mapk-dependent gene signature in colorectal cancers and provided evidence for the association of ybx1 with poor prognosis in colorectal cancer patients. this suggests that mek/erk-dependent,ybx1-regulated target genes are involved in executing malignant properties. © 2010 jürchott et al.
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آدرس
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laboratory of molecular tumor pathology,universitätsmedizin berlin,berlin, Germany, laboratory of functional genomics,universitätsmedizin berlin,berlin, Germany, laboratory of molecular tumor pathology,universitätsmedizin berlin,berlin, Germany, institute for theoretical biology,humboldt university,berlin, Germany, max delbrück center for molecular medicine,berlin, Germany, max delbrück center for molecular medicine,berlin, Germany, laboratory of molecular tumor pathology,universitätsmedizin berlin,berlin, Germany, institute for theoretical biology,humboldt university,berlin,germany,max planck institute for molecular genetics,berlin, Germany, laboratory of functional genomics,universitätsmedizin berlin,berlin, Germany, laboratory of molecular tumor pathology,universitätsmedizin berlin,berlin, Germany, institute of pathology,friedrich-schiller-university jena,jena, Germany, max delbrück center for molecular medicine,berlin,germany,charité comprehensive cancer center,berlin, Germany, max delbrück center for molecular medicine,berlin,germany,max planck institute for molecular genetics,berlin, Germany, charité comprehensive cancer center,berlin, Germany, charité comprehensive cancer center,berlin, Germany, max delbrück center for molecular medicine,berlin, Germany, max planck institute for molecular genetics,berlin, Germany, max planck institute for molecular genetics,berlin, Germany, laboratory of molecular tumor pathology,universitätsmedizin berlin,berlin, Germany, center of advanced european studies and research,bonn,germany,institute of human genetics and anthropology,heinrich-heine university düsseldorf,düsseldorf, Germany, institute for theoretical biology,humboldt university,berlin, Germany, laboratory of molecular tumor pathology,universitätsmedizin berlin,berlin,germany,laboratory of functional genomics,universitätsmedizin berlin,berlin,germany,charité comprehensive cancer center,berlin, Germany
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Authors
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