1. Transactivation of MCP-1/CCL2 by β-catenin/TCF-4 in human breast cancer cells
- Author
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Christine Gilles, Agnès Noël, Myriam Polette, Atsuhisa Ueda, Giovanna Butticè, Mélanie Mestdagt, Jean-Michel Foidart, Laboratory of Developmental and Tumour Biology (LDTB), Université de Liège, Dynamique cellulaire et moléculaire de la muqueuse respiratoire, Université de Reims Champagne-Ardenne (URCA)-IFR53-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Biochemistry, Boston University School of Medicine (BUSM), Boston University [Boston] (BU)-Boston University [Boston] (BU), Yokohama City University School of Medecine (YCUSM), Yokohama University School of Medecine, Communauté française de Belgique (Actions de Recherches Concert2es), Commission of European Communities (FP6 Brecosm), Fonds de la Recherche Scientifique Médicale, Fonds National de la Recherche Scientifique (FNRS, Belgium), Fédération Belge Contre le Cancer, C.G.R.I.-F.N.R.S.-INSERM Coopération, Fonds spéciaux de la Recherche (University of Liège, Centre Anticancéreux près l'Université de Liège, Fortis Banque Assurances, Fondation Léon Frédéricq (University of Liège), D.G.T.R.E. from the ‘‘Région Wallonne', Fonds d'Investissements de la Recherche Scientifique (CHU, Liège, Belgium), Interuniversity Attraction Poles Programme-Belgian Science Policy (Brussels, Belgium)., and Birembaut, Philippe
- Subjects
MESH: Carcinoma ,Cancer Research ,Angiogenesis ,TCF/LEF family ,medicine.disease_cause ,[SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract ,MESH: Cadherins ,MESH: Down-Regulation ,Transactivation ,0302 clinical medicine ,Tumor Cells, Cultured ,Promoter Regions, Genetic ,skin and connective tissue diseases ,Chemokine CCL2 ,beta Catenin ,0303 health sciences ,Neovascularization, Pathologic ,Transfection ,Cadherins ,MESH: Tum ,Up-Regulation ,3. Good health ,MESH: Promoter Regions (Genetics) ,Cell Transformation, Neoplastic ,Oncology ,030220 oncology & carcinogenesis ,Disease Progression ,MESH: Disease Progression ,TCF Transcription Factors ,Transcription Factor 7-Like 2 Protein ,Transcriptional Activation ,Down-Regulation ,Breast Neoplasms ,Biology ,Article ,03 medical and health sciences ,breast cancer ,Breast cancer ,medicine ,Humans ,MESH: Chemokine CCL2 ,030304 developmental biology ,MESH: Humans ,Carcinoma ,β-catenin ,medicine.disease ,MESH: Trans-Activation (Genetics) ,MESH: Cell Transformation, Neoplastic ,Tumor progression ,Cancer cell ,Cancer research ,[SDV.MHEP.PSR] Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract ,MESH: Neovascularization, Pathologic ,Carcinogenesis ,MESH: Breast Neoplasms ,MESH: TCF Transcription Factors ,MCP-1 - Abstract
International audience; The loss of E-cadherin expression and the translocation of beta-catenin to the nucleus are frequently associated with the metastatic conversion of epithelial cells. In the nucleus, beta-catenin binds to the TCF/LEF-1 (T-cell factor/ lymphoid enhancer factor) transcription factor family resulting in the activation of several genes, some of them having important implications in tumour progression. In our study, we investigated the potential regulation of monocyte chemotactic protein-1 (MCP-1/CCL2) expression by the beta-catenin/TCF pathway. This CC-chemokine has been implicated in tumour progression events such as angiogenesis or tumour associated macrophage (TAM) infiltration. We thus demonstrated that MCP-1 expression correlates with the reorganization of the E-cadherin/beta-catenin complexes. Indeed, MCP-1 was expressed by invasive breast cancer cells (MDA-MB-231, BT549 and Hs578T), which do not express E-cadherin but was not produced by noninvasive breast cancer cell lines (MCF7 and T47D) expressing high level of E-cadherin. In addition, the MCP-1 promoter was activated in BT549 breast cancer cells transfected with beta-catenin and TCF-4 cDNAs. The MCP-1 mRNA level was similarly upregulated. Moreover, we showed that MCP-1 mRNA was downregulated after transfection with a siRNA against beta-catenin in both BT549 and Hs578T cells. Our results therefore identify MCP-1 as a target of the beta-catenin/TCF/LEF pathway in breast tumour cells, a regulation which could play a key role in breast tumour progression.
- Published
- 2005