Together, these data support the possibility that crosstalk between both the PI3K/Akt and MAPK pathways and nongenomic ERα signaling may be playing a role in obesity-induced postmenopausal breast cancer progression, although the PI3K/Akt pathway may be the more important mediator of these effects. The gene discussed is ESR1; the disease is obesity due to melanocortin 4 receptor deficiency.