Genistein is another ER-β agonist, and treatments with genistein inhibited cell proliferation of human intrahepatic CCA lines (HuCCT1 and RMCCA-1) by decreasing activation of AKT and ERK1/2 signaling pathways, indicating that activation of ER-α or ER-β results in different effects in CCA cells [56]. This evidence concerns the gene ESR2 and cholangiocarcinoma.