title: The sonic hedgehog pathway as a treatment target for extrahepatic biliary             tract cancer.
abstract: Sonic hedgehog (SHh) signaling is essential for normal development of the             human gastrointestinal (GI) tract and is reported to be aberrantly activated in             GI cancers. However, the association between SHh signaling and extrahepatic biliary             tract cancer is not clearly understood. In this study, we evaluated the activities             of SHh family proteins and their downstream signals in extrahepatic biliary tract             cancer. The activity of the SHh pathway was analyzed in established human extrahepatic             biliary tract cell lines and human cancer tissues using RT-PCR and immunohistochemistry.             We also evaluated the effects of suppressing the SHh pathway with cyclopamine             and siRNA. The SHh, Smo and Gli-1 genes were overexpressed in extrahepatic biliary             tract cancer cell lines and six extrahepatic biliary tract cancer tissues compared             to the levels in normal biliary tract tissues. The degrees of SHh and Gli-1 expression             were independent of tumor stage and cancer cell differentiation. SHh pathway suppression             with cyclopamine or siRNA inhibited proliferation of extrahepatic biliary tract             cancer cell lines. In conclusion, the SHh pathway is highly activated in extrahepatic             biliary tract cancer and is a potential anticancer drug target.
authors.affiliation: Division of Gastroenterology, Department of Internal Medicine,                     Gachon University of Medicine and Science, Gil Medical Center, Incheon,                     Republic of Korea.
authors.forename: Yoon Jae
authors.initials: YJ
authors.lastname: Kim
authors.forename: Soo Bin
authors.initials: SB
authors.lastname: Park
authors.forename: Jeong Youp
authors.initials: JY
authors.lastname: Park
authors.forename: Seung Woo
authors.initials: SW
authors.lastname: Park
authors.forename: Jae Bock
authors.initials: JB
authors.lastname: Chung
authors.forename: Si Young
authors.initials: SY
authors.lastname: Song
authors.forename: Seungmin
authors.initials: S
authors.lastname: Bang
mesh_terms: D000368:Aged; D017734:Bile Ducts, Extrahepatic; D001661:Biliary Tract Neoplasms / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D005260:Female; D053823:Hedgehog Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D014157:Transcription Factors / Q000378:metabolism; D014704:Veratrum Alkaloids / Q000494:pharmacology; D000071676:Zinc Finger Protein GLI1
chemical_list: C400551:GLI1 protein, human; D053823:Hedgehog Proteins; D034741:RNA, Small Interfering; D014157:Transcription Factors; D014704:Veratrum Alkaloids; D000071676:Zinc Finger Protein GLI1; C000541:cyclopamine