GPER mechanism starts it binds to E2, inducing conformational changes that activates the trimeric G-protein that is coupled to the receptor, which induces the activation of c-Src kinase and the formation of the c-Src/PI3-K complex that favors the activation of Akt and PKCζ pathways, where Akt increases the transcription of cyclin D1, and PKCζ actives the Ras/Raf/MEK/ERK pathway, promoting the G1/S transition in cancer cells (66). The gene discussed is CCND1; the disease is cancer.