The pro‐proliferative effect of insulin in human breast epithelial DMBA‐transformed and non‐transformed cell lines is PI3K‐, mTOR‐ and GLUT1‐dependent

Abstract

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‐12ADMBA) and non‐treated breast epithelial (MCF‐12A) cell lines. Insulin (50 nM) promotes cell proliferation, 3H‐DG uptake and lactic acid production in both cell lines. The stimulatory effects of insulin upon cell proliferation and 3H‐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.