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

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.