胰岛素在人乳腺上皮 DMBA 转化和未转化细胞系中的促增殖作用依赖于 PI3K、mTOR 和 GLUT1。
The pro-proliferative effect of insulin in human breast epithelial DMBA-transformed and non-transformed cell lines is PI3K-, mTOR- and GLUT1-dependent.
机构信息
Unit of Biochemistry, Department of Biomedicine, Faculty of Medicine, University of Porto, Porto, Portugal.
Instituto de Investigação e Inovação em Saúde (i3S), University of Porto, Porto, Portugal.
出版信息
Cell Biochem Funct. 2022 Mar;40(2):127-137. doi: 10.1002/cbf.3681. Epub 2022 Jan 10.
Type 2 diabetes mellitus (T2DM) is linked to an increased risk of breast cancer. We aimed to investigate how T2DM-associated characteristics (high levels of glucose, insulin, leptin, inflammatory mediators and oxidative stress) influence breast cancer carcinogenesis, in DMBA-treated (MCF-12A ) and non-treated breast epithelial (MCF-12A) cell lines. Insulin (50 nM) promotes cell proliferation, H-DG uptake and lactic acid production in both cell lines. The stimulatory effects of insulin upon cell proliferation and H-DG uptake were hampered by rapamycin, LY294001 and BAY-876, in both cell lines. In conclusion, hyperinsulinemia, one important characteristic of T2DM, contributes to the initiation of breast cancer by a PI3K- and mTOR-dependent mechanism involving increased GLUT1-mediated glucose uptake. SIGNIFICANCE: The pro-proliferative effect of insulin in human breast epithelial DMBA-transformed and non-transformed cell lines is PI3K-, mTOR- and GLUT1-dependent.
2 型糖尿病（T2DM）与乳腺癌风险增加有关。我们旨在研究 T2DM 相关特征（高血糖、胰岛素、瘦素、炎症介质和氧化应激）如何影响 DMBA 处理（MCF-12A）和未处理的乳腺上皮（MCF-12A）细胞系中的乳腺癌发生。胰岛素（50 nM）促进两种细胞系中的细胞增殖、H-DG 摄取和乳酸生成。在两种细胞系中，雷帕霉素、LY294001 和 BAY-876 均阻碍了胰岛素对细胞增殖和 H-DG 摄取的刺激作用。总之，高胰岛素血症是 T2DM 的一个重要特征，通过涉及增加 GLUT1 介导的葡萄糖摄取的 PI3K 和 mTOR 依赖性机制，促进乳腺癌的发生。意义：胰岛素在人乳腺上皮 DMBA 转化和未转化细胞系中的促增殖作用依赖于 PI3K、mTOR 和 GLUT1。
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