In fact, while in H69 human biliary cells (both ciliated or non-ciliated), TGR5–induced proliferation is strictly related to fluctuations of cAMP levels [63], in murine cholangiocytes and human CCA cell lines (EGI-1 and TFK-1), cAMP signaling mainly contributes to apoptosis suppression, and growth is maintained by stimulation of the EGFR/ERK1/2 pathway [94]. This evidence concerns the gene MAPK3 and cholangiocarcinoma.