E2 binds GPER1 with high affinity and this activation leads to ERK phosphorylation, PI3K stimulation, intracellular Ca2+ increase, and cAMP production in the MCF-7 breast cancer cell line, which occurs via trans-activation of the epidermal growth factor receptor and results in proliferation (Filardo et al., 2000). Here, EGFR is linked to breast cancer.