ESR2 and Familial prostate cancer: On the contrary, E2 triggers, through the ERβ subtype, a pro-apoptotic effect in prostate cancer cells via the tumor necrosis factor alpha (TNFα) signaling [141], and in colon cancer cells through activating the p38/MAPK pathway [82,129], confirming the strong dependence of the effect of E2 on the balance between the expression and signaling activated by ERα or ERβ [70,79,95].