title: CtBP1 associates metabolic syndrome and breast carcinogenesis targeting multiple miRNAs.
abstract: Metabolic syndrome (MeS) has been identified as a risk factor for breast cancer. C-terminal binding protein 1 (CtBP1) is a co-repressor of tumor suppressor genes that is activated by low NAD+/NADH ratio. High fat diet (HFD) increases intracellular NADH. We investigated the effect of CtBP1 hyperactivation by HFD intake on mouse breast carcinogenesis. We generated a MeS-like disease in female mice by chronically feeding animals with HFD. MeS increased postnatal mammary gland development and generated prominent duct patterns with markedly increased CtBP1 and Cyclin D1 expression. CtBP1 induced breast cancer cells proliferation. Serum from animals with MeS enriched the stem-like/progenitor cell population from breast cancer cells. CtBP1 increased breast tumor growth in MeS mice modulating multiple genes and miRNA expression implicated in cell proliferation, progenitor cells phenotype, epithelial to mesenchymal transition, mammary development and cell communication in the xenografts. These results define a novel function for CtBP1 in breast carcinogenesis.
authors.affiliation: Laboratorio de Oncología Molecular y Nuevos Blancos Terapéuticos, Instituto de Biología y Medicina Experimental (IBYME), CONICET, Buenos Aires, Argentina.
authors.forename: Paola
authors.initials: P
authors.lastname: De Luca
authors.affiliation: Laboratorio de Oncología Molecular y Nuevos Blancos Terapéuticos, Instituto de Biología y Medicina Experimental (IBYME), CONICET, Buenos Aires, Argentina.
authors.forename: Guillermo N
authors.initials: GN
authors.lastname: Dalton
authors.affiliation: Laboratorio de Oncología Molecular y Nuevos Blancos Terapéuticos, Instituto de Biología y Medicina Experimental (IBYME), CONICET, Buenos Aires, Argentina.
authors.forename: Georgina D
authors.initials: GD
authors.lastname: Scalise
authors.affiliation: Laboratorio de Oncología Molecular y Nuevos Blancos Terapéuticos, Instituto de Biología y Medicina Experimental (IBYME), CONICET, Buenos Aires, Argentina.
authors.forename: Cristian P
authors.initials: CP
authors.lastname: Moiola
authors.affiliation: Laboratorio de Oncología Molecular y Nuevos Blancos Terapéuticos, Instituto de Biología y Medicina Experimental (IBYME), CONICET, Buenos Aires, Argentina.
authors.forename: Juliana
authors.initials: J
authors.lastname: Porretti
authors.affiliation: Laboratorio de Oncología Molecular y Nuevos Blancos Terapéuticos, Instituto de Biología y Medicina Experimental (IBYME), CONICET, Buenos Aires, Argentina.
authors.forename: Cintia
authors.initials: C
authors.lastname: Massillo
authors.affiliation: Departamento de Fisiología, Biología Molecular y Celular, Facultad de Ciencias Exactas y Naturales (FCEN), Universidad de Buenos Aires (UBA), and Instituto de Fisiología, Biología Molecular y Neurociencias (IFIBYNE), CONICET, Buenos Aires, Argentina.
authors.forename: Edith
authors.initials: E
authors.lastname: Kordon
authors.affiliation: National Cancer Institute and National Institute of Minority Health and Disparities, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Kevin
authors.initials: K
authors.lastname: Gardner
authors.affiliation: Laboratorio de Oncología Molecular y Nuevos Blancos Terapéuticos, Instituto de Biología y Medicina Experimental (IBYME), CONICET, Buenos Aires, Argentina.
authors.forename: Florencia
authors.initials: F
authors.lastname: Zalazar
authors.affiliation: Área de Investigación del Instituto de Oncología A.H. Roffo, Universidad de Buenos Aires, Buenos Aires, Argentina.
authors.forename: Carolina
authors.initials: C
authors.lastname: Flumian
authors.affiliation: Área de Investigación del Instituto de Oncología A.H. Roffo, Universidad de Buenos Aires, Buenos Aires, Argentina.
authors.forename: Laura
authors.initials: L
authors.lastname: Todaro
authors.affiliation: Laboratorio de Inflamación y Cáncer, Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales (FCEN), Universidad de Buenos Aires (UBA), IQUIBICEN - CONICET, Buenos Aires, Argentina.
authors.forename: Elba S
authors.initials: ES
authors.lastname: Vazquez
authors.affiliation: Departamento de Patología, Instituto de Estudios Oncológicos, Academia Nacional de Medicina, Buenos Aires, Argentina.
authors.forename: Roberto
authors.initials: R
authors.lastname: Meiss
authors.affiliation: Laboratorio de Oncología Molecular y Nuevos Blancos Terapéuticos, Instituto de Biología y Medicina Experimental (IBYME), CONICET, Buenos Aires, Argentina.
authors.forename: Adriana
authors.initials: A
authors.lastname: De Siervi
mesh_terms: D000429:Alcohol Oxidoreductases / Q000378:metabolism*; D000818:Animals; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D059305:Diet, High-Fat; D005260:Female; D064593:Heterografts; D006801:Humans; D061986:MCF-7 Cells; D024821:Metabolic Syndrome / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008819:Mice, Nude; D035683:MicroRNAs / Q000378:metabolism*; D041681:NIH 3T3 Cells; D011897:Random Allocation; D012307:Risk Factors
chemical_list: D004268:DNA-Binding Proteins; D035683:MicroRNAs; D000429:Alcohol Oxidoreductases; C096794:C-terminal binding protein
keywords: CtBP1; breast cancer; high fat diet; metabolic syndrome; miRNAs