title: Establishment and characterisation of six human biliary tract cancer cell lines.
abstract: Human cell lines established from biliary tract cancers are rare, and only five have been reported previously. We report the characterisation of six new six biliary tract cancer cell lines (designated SNU-245, SNU-308, SNU-478, SNU-869, SNU-1079 and SNU-1196) established from primary tumour samples of Korean patients. The cell lines were isolated from two extrahepatic bile duct cancers (one adenocarcinoma of common bile duct, one hilar bile duct cancer), two adenocarcinomas of ampulla of Vater, one intrahepatic bile duct cancer (cholangiocarcinoma), and one adenocarcinoma of the gall bladder. The cell phenotypes, including the histopathology of the primary tumours and in vitro growth characteristics, were determined. We also performed molecular characterisation, including DNA fingerprinting analysis and abnormalities of K-ras, p15, p16, p53, hMLH1, hMSH2, DPC4, beta-catenin, E-cadherin, hOGG1, STK11, and TGF-betaRII genes by PCR-SSCP and sequencing analysis. In addition, we compared the genetic alterations in tumour cell lines and their corresponding tumour tissues. All lines grew as adherent cells. Population doubling times varied from 48-72 h. The culture success rate was 20% (six out of 30 attempts). All cell lines showed (i) relatively high viability; (ii) absence of mycoplasma or bacteria contamination; and (iii) genetic heterogeneity by DNA fingerprinting analysis. Among the lines, three lines had p53 mutations; and homozygous deletions in both p16 and p15 genes were found three and three lines, respectively; one line had a heterozygous missense mutation in hMLH1; E-cadherin gene was hypermethylated in two lines. Since the establishment of biliary tract cancer cell lines has been rarely reported in the literature, these newly established and well characterised biliary tract cancer cell lines would be very useful for studying the biology of biliary tract cancers, particularly those related to hypermethylation of E-cadherin gene in biliary tract cancer.
authors.affiliation: Laboratory of Cell Biology, Korean Cell Line Bank, Cancer Research Center and Cancer Research Institute, Seoul National University College of Medicine, Seoul 110-744, Korea.
authors.forename: J-L
authors.initials: JL
authors.lastname: Ku
authors.forename: K-A
authors.initials: KA
authors.lastname: Yoon
authors.forename: I-J
authors.initials: IJ
authors.lastname: Kim
authors.forename: W-H
authors.initials: WH
authors.lastname: Kim
authors.forename: J-Y
authors.initials: JY
authors.lastname: Jang
authors.forename: K-S
authors.initials: KS
authors.lastname: Suh
authors.forename: S-W
authors.initials: SW
authors.lastname: Kim
authors.forename: Y-H
authors.initials: YH
authors.lastname: Park
authors.forename: J-H
authors.initials: JH
authors.lastname: Hwang
authors.forename: Y-B
authors.initials: YB
authors.lastname: Yoon
authors.forename: J-G
authors.initials: JG
authors.lastname: Park
mesh_terms: D000091162:AMP-Activated Protein Kinase Kinases; D048868:Adaptor Proteins, Signal Transducing; D000230:Adenocarcinoma / Q000235:genetics / Q000473:pathology*; D014670:Ampulla of Vater; D001650:Bile Duct Neoplasms / Q000235:genetics / Q000473:pathology; D001661:Biliary Tract Neoplasms / Q000235:genetics / Q000473:pathology*; D015820:Cadherins / Q000235:genetics; D002352:Carrier Proteins; D002448:Cell Adhesion; D018797:Cell Cycle Proteins / Q000235:genetics; D018281:Cholangiocarcinoma / Q000235:genetics / Q000473:pathology*; D003138:Common Bile Duct Neoplasms / Q000235:genetics / Q000473:pathology; D050762:Cyclin-Dependent Kinase Inhibitor p15; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics; D003598:Cytoskeletal Proteins / Q000235:genetics; D016172:DNA Fingerprinting; D019175:DNA Methylation; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics; D043382:DNA-Formamidopyrimidine Glycosylase; D005706:Gallbladder Neoplasms / Q000235:genetics / Q000473:pathology; D017353:Gene Deletion; D020868:Gene Silencing; D019942:Genes, p16; D016158:Genes, p53; D011905:Genes, ras; D006801:Humans; D000070957:MutL Protein Homolog 1; D009699:N-Glycosyl Hydrolases / Q000235:genetics; D009363:Neoplasm Proteins / Q000032:analysis* / Q000235:genetics; D009687:Nuclear Proteins; D017346:Protein Serine-Threonine Kinases / Q000235:genetics; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics; D051901:Smad4 Protein; D015534:Trans-Activators / Q000235:genetics; D014407:Tumor Cells, Cultured / Q000737:chemistry / Q000473:pathology; D025521:Tumor Suppressor Proteins; D051176:beta Catenin
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C493966:CDKN2B protein, human; C495270:CTNNB1 protein, human; D015820:Cadherins; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D050762:Cyclin-Dependent Kinase Inhibitor p15; D019941:Cyclin-Dependent Kinase Inhibitor p16; D003598:Cytoskeletal Proteins; D004273:DNA, Neoplasm; D004268:DNA-Binding Proteins; C501486:MLH1 protein, human; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D018125:Receptors, Transforming Growth Factor beta; C497796:SMAD4 protein, human; D051901:Smad4 Protein; D015534:Trans-Activators; D025521:Tumor Suppressor Proteins; D051176:beta Catenin; D017346:Protein Serine-Threonine Kinases; C109790:STK11 protein, human; D000091162:AMP-Activated Protein Kinase Kinases; D000077294:Receptor, Transforming Growth Factor-beta Type II; D009699:N-Glycosyl Hydrolases; D043382:DNA-Formamidopyrimidine Glycosylase; D000070957:MutL Protein Homolog 1