Abstract
Despite advances in diagnosis and treatment, the prognosis of cholangiocarcinoma has not yet been resolved. To improve the prognosis, we require a fuller understanding of the molecular mechanisms behind its proliferation and progression. We have shown that exogenous HGF and IL6 are also mitogenic for cholangiocarcinoma cells, and neoplastic transformation is associated with constitutive production of these growth factors. We also demonstrated that cholangiocarcinoma cells produced TGFβ and demonstrated accelerated growth in the presence of TGFβ1 with no apoptotic effect. Furthermore, we demonstrated that short hairpin RNA targeting TGFβ receptor II can be used to silence TGFβ receptor II genes in mouse cell lines, and physiologic changes in mice suffering from acute liver injury are spared by RNAi-mediated gene silencing and by suppressing downstream signal transduction. Further efforts to elucidate the underlying molecular in cholangiocarcinogenesis may afford an important opportunity to define a novel molecular target for cholangiocarcinoma prevention and treatment.
