title: Establishment and characterization of unique human gallbladder cancer cell lines.
abstract: Gallbladder cancer has a dismal prognosis. Understanding the disease at the biological, genetic, molecular, cellular, and clinical level is essential for effective diagnostics and therapeutics. However, the currently established gallbladder cell lines are insufficient for better understanding and further research. The aim of our present study was to establish and characterize human gallbladder cancer cell lines. We established 5 cell lines from resected specimens of gallbladder cancers. These cell lines revealed typical tumor histopathological characteristics. We examined growth characteristics and the colony-forming ability of established cell lines in terms of their cell cycle parameters, expression of tumor markers (carcinoembryonic antigen; CEA, carbohydrated antigen 19-9; CA19-9, MUC-1 and c-kit) and the oncogene c-erbB2 by flow cytometer. Comparative genomic hybridization (CGH) analysis with specific gene probes was performed to detect changes in the gene copy numbers. Human origin of cell lines was confirmed by chromosomal analysis. Cells maintained differentiation characteristics of the original tumors. The doubling time of different cell lines varied from 30 to 96 h. All 5 cell lines formed colonies in the colony forming assays and expressed CEA, CA19-9, MUC-1 and the oncogene c-erbB2 and showed chromosomal aneuploidy. CGH analysis demonstrated gain of chromosomal region bearing SRC, RAB1, and PAP in all cell lines and hTERT in 4 cell lines. These newly established cell lines might serve as a useful model for studying the molecular pathogenesis of gallbladder cancer. Furthermore, they may serve as a model for testing new therapeutics against gallbladder cancer. These chromosomal aberrations and imbalances provide a starting point for molecular analyses of genomic regions and genes in gallbladder carcinogenesis.
authors.affiliation: Department of Surgery, Institute of Clinical Medicine, University of Tsukuba, Tsukuba-shi, Japan.
authors.forename: Mila
authors.initials: M
authors.lastname: Ghosh
authors.forename: Naoto
authors.initials: N
authors.lastname: Koike
authors.forename: Go
authors.initials: G
authors.lastname: Yanagimoto
authors.forename: Shin-Ichi
authors.initials: S
authors.lastname: Tsunoda
authors.forename: Sunil
authors.initials: S
authors.lastname: Kaul
authors.forename: Takashi
authors.initials: T
authors.lastname: Hirano
authors.forename: Fabian
authors.initials: F
authors.lastname: Emura
authors.forename: Hironobu
authors.initials: H
authors.lastname: Kashiwagi
authors.forename: Toru
authors.initials: T
authors.lastname: Kawamoto
authors.forename: Nobuhiro
authors.initials: N
authors.lastname: Ohkohchi
authors.forename: Kaoru
authors.initials: K
authors.lastname: Saijo
authors.forename: Tadao
authors.initials: T
authors.lastname: Ohno
authors.forename: Masanao
authors.initials: M
authors.lastname: Miwa
authors.forename: Takeshi
authors.initials: T
authors.lastname: Todoroki
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor / Q000378:metabolism*; D018395:CA-19-9 Antigen / Q000378:metabolism; D002272:Carcinoembryonic Antigen / Q000378:metabolism; D002453:Cell Cycle; D002455:Cell Division; D002869:Chromosome Aberrations; D003114:Colony-Forming Units Assay; D005706:Gallbladder Neoplasms / Q000378:metabolism / Q000473:pathology*; D005784:Gene Amplification; D018628:Gene Dosage; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D018396:Mucin-1 / Q000378:metabolism; D009693:Nucleic Acid Hybridization; D019009:Proto-Oncogene Proteins c-kit / Q000378:metabolism; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D014407:Tumor Cells, Cultured
chemical_list: D014408:Biomarkers, Tumor; D018395:CA-19-9 Antigen; D002272:Carcinoembryonic Antigen; D018396:Mucin-1; D019009:Proto-Oncogene Proteins c-kit; D018719:Erb-b2 Receptor Tyrosine Kinases