CtBP1 associates metabolic syndrome and breast carcinogenesis targeting multiple miRNAs.

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

doi:10.18632/oncotarget.7711

Paola De Luca, Carolina Flumian + Show 12 more

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https://doi.org/10.18632/oncotarget.7711

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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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Breast cancer is the leading cause of cancer death among women, after skin cancers [1]
It is estimated that around 30% of total cancer deaths in United States could be attributed to life style, diet and physical activity; all factors associated to metabolic syndrome (MeS) [4]
To analyze the involvement of C-terminal binding protein 1 (CtBP1) in breast carcinogenesis, female nu/nu mice were chronically fed with High fat diet (HFD) or control diet (CD)

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Introduction

Breast cancer is the leading cause of cancer death among women, after skin cancers [1]. It is estimated that around 30% of total cancer deaths in United States could be attributed to life style, diet and physical activity; all factors associated to metabolic syndrome (MeS) [4]. Several studies have established that components of MeS are positively correlated with breast cancer development [6,7,8,9]. MeS has been associated with breast cancer risk in women, and this correlation is stronger within postmenopausal population [10,11,12]

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