Characterization and genetic analysis in the newly established human bile duct cancer cell lines.
Bile duct carcinoma patients generally have a poor prognosis. Understanding this cancer at the biological, genetic, molecular, and cellular level in ways relevant to clinical management is essential for developing effective preventive and therapeutic regimens. However, the currently established bile duct cancer cell lines are still insufficient for the research required to attain such an improved understanding. The aim of this study was to establish and characterize human bile duct cancer cell lines. We examined the growth characteristics and colony-forming ability of the established cell lines in terms of their cell cycle parameters and expression of tumor markers (CEA, CA19-9, MUC-1 and c-kit) and oncogene (c-erbB2) by flow cytometry. Comparative genomic hybridization (CGH) was performed to detect changes in the gene copy numbers. Human origin of the cell lines was confirmed by chromosomal analysis. We have established 3 cell lines and designated them as TGBC-47, TGBC-51, and TBCN-6 and the population doubling times of the three cell lines were 28, 38 and 94 h, respectively. The cells maintained differentiation characteristics of the original tumors. Two cell lines formed colonies in the colony forming assays; all three-cell lines expressed CEA, CA19-9, MUC-1 and c-erbB2 and showed chromosomal aneuploidy. CGH analysis demonstrated gains in various chromosomal regions, including 1q, 5p, 6p, 7q and 8q in two cell lines, and the loss in 17p in three cell lines. These newly established cell lines might serve as useful models for studying the advanced molecular tumor biology of bile duct cancer. Furthermore, they may assist translational research in the development of new effective molecular targeting chemoradiotherapy regimens. These chromosomal aberrations and imbalances provide some starting points for the molecular analysis of genomic regions and genes involved in bile duct carcinogenesis.
Ghosh
Mila
M
Department of Surgery, Institute of Clinical Medicine, University of Tsukuba, Tsukuba-Shi 305-8575, Japan.
Koike
Naoto
N
Tsunoda
Shin-Ichi
S
Hirano
Takashi
T
Kaul
Sunil
S
Kashiwagi
Hironobu
H
Kawamoto
Toru
T
Ohkohchi
Nobuhiro
N
Saijo
Kaoru
K
Ohno
Tadao
T
Miwa
Masanao
M
Todoroki
Takeshi
T
D001650:Bile Duct Neoplasms / Q000235:genetics* / Q000378:metabolism; D018395:CA-19-9 Antigen / Q000096:biosynthesis; D002272:Carcinoembryonic Antigen / Q000096:biosynthesis; D002453:Cell Cycle; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002469:Cell Separation; D002875:Chromosomes / Q000648:ultrastructure; D005434:Flow Cytometry; D006801:Humans; D007621:Karyotyping; D008854:Microscopy, Electron; D008858:Microscopy, Phase-Contrast; D018396:Mucin-1 / Q000096:biosynthesis; D009693:Nucleic Acid Hybridization; D011379:Prognosis; D011863:Radioimmunoassay; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000096:biosynthesis; D013997:Time Factors
D018395:CA-19-9 Antigen; D002272:Carcinoembryonic Antigen; D018396:Mucin-1; D018719:Erb-b2 Receptor Tyrosine Kinases