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Sonic hedgehog (SHh) signaling is essential for normal development of thehuman gastrointestinal (GI) tract and is reported to be aberrantly activated inGI cancers. However, the association between SHh signaling and extrahepatic biliarytract cancer is not clearly understood. In this study, we evaluated the activitiesof SHh family proteins and their downstream signals in extrahepatic biliary tractcancer. The activity of the SHh pathway was analyzed in established human extrahepaticbiliary tract cell lines and human cancer tissues using RT-PCR and immunohistochemistry.We also evaluated the effects of suppressing the SHh pathway with cyclopamineand siRNA. The SHh, Smo and Gli-1 genes were overexpressed in extrahepatic biliarytract cancer cell lines and six extrahepatic biliary tract cancer tissues comparedto the levels in normal biliary tract tissues. The degrees of SHh and Gli-1 expressionwere independent of tumor stage and cancer cell differentiation. SHh pathway suppressionwith cyclopamine or siRNA inhibited proliferation of extrahepatic biliary tractcancer cell lines. In conclusion, the SHh pathway is highly activated in extrahepaticbiliary tract cancer and is a potential anticancer drug target.

The sonic hedgehog pathway as a treatment target for extrahepatic biliary tract cancer