GPER-1 was also reported to be activated through estrogen-mediated extracellular signal-regulated kinase 1/2 (ERK1/2) and increase the concentration of cAMP in breast cancers, which further activates protein kinase A (PKA) and phosphorylates cAMP response element-binding protein (CREB) [23,24]. This evidence concerns the gene MAPK3 and breast cancer.