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Transcriptional activation of interleukin-8 by beta-catenin-Tcf4

Title: Transcriptional activation of interleukin-8 by beta-catenin-Tcf4
Authors: Levy, L.; Neuveut, C.; Renard, C. A.; Charneau, P.; Branchereau, S.; Gauthier, F.; van Nhieu, J. T.; Cherqui, D.; Petit-Bertron, A. F.; Mathieu, D.; Buendia, M. A.
Contributors: Recombinaison et Expression Génétique; Institut Pasteur Paris (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM); Cytokines et Inflammation; Institut Pasteur Paris (IP); Virologie moléculaire et Vectorologie; Institut Pasteur Paris (IP)-Centre National de la Recherche Scientifique (CNRS); Hôpital Bicêtre AP-HP, Le Kremlin-Bicêtre; Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP); Hôpital Henri Mondor; Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Henri Mondor Créteil; Groupe Henri Mondor-Albert Chenevier-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Henri Mondor-Albert Chenevier-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12); Institut de Génétique Moléculaire de Montpellier (IGMM); Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS); This work was supported in part by the Association pour la Recherche sur le Cancer (ARC) (to L. L.) and by Grant 5236 from the ARC.The costs of publication of this article were defrayed in part by the payment of page charges.; We thank Drs. H. Clevers, J. Hulsken, and Y. Nakatani for providing plasmids and Julien Pothlichet for help as a graduate student. We are grateful to Pierre Tiollais for constant interest in this work.
Source: ISSN: 0021-9258.
Publisher Information: CCSD; American Society for Biochemistry and Molecular Biology
Publication Year: 2002
Collection: Université de Montpellier: HAL
Subject Terms: [SDV.BBM]Life Sciences [q-bio]/Biochemistry; Molecular Biology
Description: International audience ; 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 Writ 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.
Document Type: article in journal/newspaper
Language: English
Relation: info:eu-repo/semantics/altIdentifier/pmid/12200448; PUBMED: 12200448
DOI: 10.1074/jbc.M207418200
Availability: https://hal.science/hal-02197533; https://hal.science/hal-02197533v1/document; https://hal.science/hal-02197533v1/file/PIIS0021925819720985.pdf; https://doi.org/10.1074/jbc.M207418200
Rights: https://creativecommons.org/licenses/by/4.0/ ; info:eu-repo/semantics/OpenAccess
Accession Number: edsbas.57F89F03
Database: BASE