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Oncotarget. 2016 Apr 5;7(14):18798-811. doi: 10.18632/oncotarget.7711.

CtBP1 associates metabolic syndrome and breast carcinogenesis targeting multiple miRNAs.

Author information

1
Laboratorio de Oncología Molecular y Nuevos Blancos Terapéuticos, Instituto de Biología y Medicina Experimental (IBYME), CONICET, Buenos Aires, Argentina.
2
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.
3
National Cancer Institute and National Institute of Minority Health and Disparities, National Institutes of Health, Bethesda, MD, USA.
4
Área de Investigación del Instituto de Oncología A.H. Roffo, Universidad de Buenos Aires, Buenos Aires, Argentina.
5
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.
6
Departamento de Patología, Instituto de Estudios Oncológicos, Academia Nacional de Medicina, Buenos Aires, Argentina.

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.

KEYWORDS:

CtBP1; breast cancer; high fat diet; metabolic syndrome; miRNAs

PMID:
26933806
PMCID:
PMC4951330
DOI:
10.18632/oncotarget.7711
[Indexed for MEDLINE]
Free PMC Article

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