RRC ID 43851
著者 Igarashi S, Matsubara T, Harada K, Ikeda H, Sato Y, Sasaki M, Matsui O, Nakanuma Y.
タイトル Bile duct expression of pancreatic and duodenal homeobox 1 in perihilar cholangiocarcinogenesis.
ジャーナル Histopathology
Abstract AIMS: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.
METHODS AND 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.
CONCLUSION: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.
巻・号 61(2)
ページ 266-76
公開日 2012-8-1
DOI 10.1111/j.1365-2559.2012.04218.x
PMID 22594685
MeSH Adult Aged Aged, 80 and over Base Sequence Bile Duct Neoplasms / genetics Bile Duct Neoplasms / metabolism* Bile Duct Neoplasms / pathology Bile Ducts / embryology Bile Ducts / metabolism Bile Ducts / pathology Bile Ducts, Intrahepatic* Biomarkers, Tumor / genetics Biomarkers, Tumor / metabolism* Carcinoma in Situ / genetics Carcinoma in Situ / metabolism Carcinoma in Situ / pathology Carcinoma, Pancreatic Ductal / genetics Carcinoma, Pancreatic Ductal / metabolism Carcinoma, Pancreatic Ductal / pathology Cell Line, Tumor Cell Proliferation Cholangiocarcinoma / genetics Cholangiocarcinoma / metabolism* Cholangiocarcinoma / pathology Cholangitis, Sclerosing / genetics Cholangitis, Sclerosing / metabolism Cholangitis, Sclerosing / pathology Cholelithiasis / genetics Cholelithiasis / metabolism Cholelithiasis / pathology Female Fetus / metabolism Gene Knockdown Techniques Homeodomain Proteins / antagonists & inhibitors Homeodomain Proteins / genetics Homeodomain Proteins / metabolism* Humans Immunohistochemistry Liver / embryology Liver / metabolism Liver / pathology Male Middle Aged Pancreatic Neoplasms / genetics Pancreatic Neoplasms / metabolism Pancreatic Neoplasms / pathology RNA, Messenger / genetics RNA, Messenger / metabolism RNA, Neoplasm / genetics RNA, Neoplasm / metabolism Trans-Activators / antagonists & inhibitors Trans-Activators / genetics Trans-Activators / metabolism* Up-Regulation
IF 3.626
引用数 7
WOS 分野 PATHOLOGY CELL BIOLOGY
リソース情報
ヒト・動物細胞