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Transcriptional activation of interleukin-8 by beta-catenin-Tcf4 总被引:18,自引:0,他引:18
Lévy L Neuveut C Renard CA Charneau P Branchereau S Gauthier F Van Nhieu JT Cherqui D Petit-Bertron AF Mathieu D Buendia MA 《The Journal of biological chemistry》2002,277(44):42386-42393
Nuclear translocation of beta-catenin and its association with Tcf/Lef factors are key steps in transduction of the Wnt signal, which is aberrantly activated in a variety of human cancers. In a search for new beta-catenin-Tcf target genes, we analyzed beta-catenin-induced alterations of gene expression in primary human hepatocytes, after transduction of either dominant stable beta-catenin or its truncated, transactivation-deficient counterpart by means of a lentiviral vector. cDNA microarray analysis revealed a limited set of up-regulated genes, including known Wnt targets such as matrilysin and keratin-1. In this screen, we identified the CXC chemokine interleukin 8 (IL-8) as a direct target of beta-catenin-Tcf4. IL-8 is constitutively expressed in various cancers, and it has been implicated in tumor progression through its mitogenic, motogenic, and angiogenic activities. The IL-8 promoter contains a unique consensus Tcf/Lef site that is critical for IL-8 activation by beta-catenin. We show here that the p300 coactivator was required for efficient transactivation of beta-catenin on this promoter. Ectopic expression of beta-catenin in hepatoma cells promoted IL-8 secretion, which stimulated endothelial cell migration. These data define IL-8 as a Wnt target and suggest that IL-8 induction by beta-catenin might be implicated in developmental and tumorigenic processes. 相似文献
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The beta-catenin/T-cell factor/lymphocyte enhancer factor signaling pathway is required for normal and stress-induced cardiac hypertrophy
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Chen X Shevtsov SP Hsich E Cui L Haq S Aronovitz M Kerkelä R Molkentin JD Liao R Salomon RN Patten R Force T 《Molecular and cellular biology》2006,26(12):4462-4473