Research Papers:

CtBP1 associates metabolic syndrome and breast carcinogenesis targeting multiple miRNAs

Paola De Luca, Guillermo N. Dalton, Georgina D. Scalise, Cristian P. Moiola, Juliana Porretti, Cintia Massillo, Edith Kordon, Kevin Gardner, Florencia Zalazar, Carolina Flumian, Laura Todaro, Elba S. Vazquez, Roberto Meiss and Adriana De Siervi _

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Oncotarget. 2016; 7:18798-18811. https://doi.org/10.18632/oncotarget.7711

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Paola De Luca1, Guillermo N. Dalton1, Georgina D. Scalise1, Cristian P. Moiola1, Juliana Porretti1, Cintia Massillo1, Edith Kordon2, Kevin Gardner3, Florencia Zalazar1, Carolina Flumian4, Laura Todaro4, Elba S. Vazquez5, Roberto Meiss6, Adriana De Siervi1

1Laboratorio de Oncología Molecular y Nuevos Blancos Terapéuticos, Instituto de Biología y Medicina Experimental (IBYME), CONICET, Buenos Aires, Argentina

2Departamento 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

3National Cancer Institute and National Institute of Minority Health and Disparities, National Institutes of Health, Bethesda, MD, USA

4Área de Investigación del Instituto de Oncología A.H. Roffo, Universidad de Buenos Aires, Buenos Aires, Argentina

5Laboratorio 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

6Departamento de Patología, Instituto de Estudios Oncológicos, Academia Nacional de Medicina, Buenos Aires, Argentina

Correspondence to:

Adriana De Siervi, email: adrianadesiervi@gmail.com

Keywords: CtBP1, metabolic syndrome, high fat diet, breast cancer, miRNAs

Received: December 22, 2015     Accepted: February 11, 2016     Published: February 25, 2016


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.

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