title: Bile duct expression of pancreatic and duodenal homeobox 1 in perihilar cholangiocarcinogenesis.
abstract: OBJECTIVE
  Pancreatic and duodenal homeobox 1 (Pdx1) is a transcription factor that is crucial in embryogenic development and differentiation of pancreas, and its overexpression is reportedly involved in the progression of many malignancies, including pancreatic carcinoma. In this study, the role of Pdx1 was examined in cholangiocarcinogenesis.
  
  
  RESULTS
  Forty-three cases of human cholangiocarcinoma (CC) and 66 cases of hepatolithiasis or primary sclerosing cholangitis (PSC) with biliary intraepithelial neoplasia (BilIN) lesions and also eight fetal and 20 adult normal livers were examined immunohistochemically. Pdx1 was constantly expressed in the nuclei of fetal bile ducts, but was virtually absent in the large bile ducts of adults. By contrast, Hairy and enhancer of split 1 (Hes1), which represses pancreatic exocrine and endocrine differentiation, was expressed frequently in the adult bile ducts. Pdx1 was expressed in 67% of invasive CCs. In large bile ducts, expression of Pdx1 increased while that of Hes1 decreased during the progression of BilIN lesions to CC. Expression of Pdx1 correlated with proliferative activities in CCs. In an in vitro study, all three CC cell lines expressed Pdx1 mRNA and protein.
  
  
  CONCLUSIONS
  Up-regulation of Pdx1 is a feature of cholangiocarcinogenesis associated with chronic cholangitis. Furthermore, expression of Pdx1 in CC is related to increased proliferative activity in CCs.
authors.affiliation: Department of Human Pathology, Kanazawa University Graduate School of Medicine, Kanazawa, Japan.
authors.forename: Saya
authors.initials: S
authors.lastname: Igarashi
authors.forename: Takashi
authors.initials: T
authors.lastname: Matsubara
authors.forename: Kenichi
authors.initials: K
authors.lastname: Harada
authors.forename: Hiroko
authors.initials: H
authors.lastname: Ikeda
authors.forename: Yasunori
authors.initials: Y
authors.lastname: Sato
authors.forename: Motoko
authors.initials: M
authors.lastname: Sasaki
authors.forename: Osamu
authors.initials: O
authors.lastname: Matsui
authors.forename: Yasuni
authors.initials: Y
authors.lastname: Nakanuma
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001483:Base Sequence; D001650:Bile Duct Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D001652:Bile Ducts / Q000196:embryology / Q000378:metabolism / Q000473:pathology; D001653:Bile Ducts, Intrahepatic; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D002278:Carcinoma in Situ / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D021441:Carcinoma, Pancreatic Ductal / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D018281:Cholangiocarcinoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D015209:Cholangitis, Sclerosing / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D002769:Cholelithiasis / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D005260:Female; D005333:Fetus / Q000378:metabolism; D055785:Gene Knockdown Techniques; D018398:Homeodomain Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D008099:Liver / Q000196:embryology / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012334:RNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D015534:Trans-Activators / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D014408:Biomarkers, Tumor; D018398:Homeodomain Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D015534:Trans-Activators; C084010:pancreatic and duodenal homeobox 1 protein