Subsequent studies further demonstrated that estrogen binds to ERs which directly interacts with membrane receptors (such as IGFR, EGFR, and HER2) and key signaling molecules (Shc) to activate the major second messenger and MAPK, PI3K/AKT pathways and to promote the proliferation, growth, and survival of tumor cells. The gene discussed is AKT1; the disease is neoplasm.