Signaling regulation of genomic and nongenomic functions of estrogen receptors.

Estrogen receptors (ERs) mediate the effects of 17beta-estradiol under physiologic and pathologic conditions. ERs trigger 17beta-estradiol-sensitive gene transcription by binding to specific estrogen response elements (i.e. genomic mechanism). The cellular effects of estrogen are also influenced by membrane- or cytoplasm-initiated responses (i.e. nongenomic mechanism). Both ER-evoked genomic and nongenomic effects originate from a unique signaling network. Furthermore, estrogen-initiated rapid pathways and ERalpha interactions with specific partners (e.g. AIB1, PELP1/MNAR; MTA1, MTA1s and p130Cas) influence both ER functions. Here, we summarize the recent findings related to multiple regulatory levels of the signaling networks responsible for ERs-mediated responses in breast cancer cells.