Fig. 1.

Estrogen receptor signaling pathways. E2-ERα signaling pathway involving both genomic and extranuclear signaling pathways. In the genomic pathway, E2 bind to ERα and relocalizes ER to ERE elements and promotes target genes expression. In the extranuclear signaling pathways, Rapid E2 signaling activates PI3K/Akt/mTOR and eRK/MAPK pathway. PI3K/Akt/mTOR and ERK/MAPK signals can transduction genomic signals. MAPK pathway regulates SP1, c-Jun, c-Fos et al. transcription; Akt pathway regulates GATA-4, NFAT, NF-κB and other transcriptional factors; mTOR pathway regulates HP1α, PPARr, PGC1-α and other transcriptional factors. Rapid E2 signaling activates mTOR pathway also regulates protein synthesis via 4-EBP1, S6K, and others. Growth factor such as EGFR, HER2, and IGF1R crosstalk with E2/ER signaling in the extranuclear signaling pathways. E2/ER signal regulates cell proliferation, apoptosis, and cell cycle, following control cell or tissue growth