Several studies have shown that E2 triggers a variety of intracellular signaling events, including mobilization of intracellular calcium in MCF-7 breast cancer cells (23), production of cyclic adenosine monophosphate (cAMP) in primary rat uterine cells (24), activation of mitogen-activated protein kinases p38 in MCF-7 cells and ROS17/2.8 rat bone cell line (25, 26), and activation of extracellular signal-regulated kinase 1/2 (ERK 1/2) in human neuroblastoma cells (27). The gene discussed is MAPK3; the disease is breast cancer.