To understand the pathways that mediate GPER activation regulated cell proliferation, we next examined the effects of G-1 on extracellular signal-regulated protein kinases (ERKs)-1 and 2 (ERK1/2) and Akt – two signaling systems that powerfully impact cell proliferation in breast and prostate cancer cells [25]–[27]. Here, MAPK3 is linked to prostate cancer.