Estrogens receptors, steroid hormones, play a key role in many cell processes such as cell growth and cell differentiation. A number of cellular signaling pathways influence the ER-dependent gene expression modulating ER conformational changes or co-regulators recruitment. ER alpha not only can be activated by EGF, but can be activated by other growth factors including insulin, insulin-like growth factor-1 (IGF-1) and TGF-beta. In addition, heregulin, interleukin-2, and dopamine can also modulate ER activity. The phosphorylation of co-activators (SRC-1 and SRC-2) by MAPK pathway results in a general reduction in ER alpha transcriptional activity.
