Molecular aspects linking insulin resistance to breast cancer by activation of cell signalling pathways.

Recent findings suggest a connection between obesity and breast cancer. Obesity is linked with higher incidences of insulin resistance as part of the metabolic syndrome, resulting in chronically elevated insulin plasma levels. We examined the effect of high insulin concentrations (100 nM) on estrogen-receptor (ER) negative breast cancer cells (MDA-MB-231) and normal breast epithelial cells (MCF-10a). Treatment with high insulin concentrations increased insulin receptor (IR) phosphorylation significantly in both cell lines. Phosphorylation of protein kinase B (Akt), representative of PI3-kinase cell signalling pathway activation was increased by 101% (p=0.0112) in MDA-MB-231 cells and by 81% (p=0.0031) in MCF-10a cells after 10 min insulin treatment. Phosphorylation of extracellular regulated kinase 1/2 (ERK1/2), representative of MAP-kinase cell signalling pathway activation did not change in both cell lines after 10 min of insulin treatment. Cell proliferation did not change in MDA-MB-231 cells and increased by 75% (p=0.0067) in MCF-10a cells after 24 h insulin treatment. Cell proliferation was decreased in MDA-MB-231 cells by 15% (p=0.0083) after 1 h treatment with PD98059, a MAP-kinase inhibitor. In MCF-10a cells cell proliferation was decreased by 51% (