CtBP1 associates metabolic syndrome and breast carcinogenesis targeting multiple miRNAs.
CtBP1 associates metabolic syndrome and breast carcinogenesis targeting multiple miRNAs.
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DOI：
10.18632/oncotarget.7711
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发表时间：
2016-04-05
期刊：
影响因子：
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通讯作者：
De Siervi A
中科院分区：
文献类型：
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作者：
De Luca P;Dalton GN;Scalise GD;Moiola CP;Porretti J;Massillo C;Kordon E;Gardner K;Zalazar F;Flumian C;Todaro L;Vazquez ES;Meiss R;De Siervi A
代谢综合征（MeS）已被确定为乳腺癌的危险因素。c -末端结合蛋白1 （CtBP1）是肿瘤抑制基因的共同抑制因子，在低NAD+/NADH比例下被激活。高脂肪饮食（HFD）增加细胞内NADH。我们研究了摄入HFD后CtBP1过度激活对小鼠乳腺癌发生的影响。我们通过长期喂养患有HFD的动物，在雌性小鼠中产生了mes样疾病。MeS增加了出生后乳腺的发育，并产生了突出的导管模式，CtBP1和Cyclin D1的表达显著增加。CtBP1诱导乳腺癌细胞增殖。具有MeS的动物血清富集了乳腺癌细胞的干细胞样/祖细胞群。CtBP1增加了MeS小鼠乳腺肿瘤的生长，调节了与细胞增殖、祖细胞表型、上皮细胞向间充质细胞转化、乳腺发育和细胞通讯有关的多个基因和miRNA的表达。这些结果确定了CtBP1在乳腺癌发生中的新功能。
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.