title: Establishment and characterization of four malignant pleural mesothelioma cell lines from Japanese patients.
abstract: Malignant pleural mesothelioma (MPM) is an asbestos-related malignancy that is highly resistant to current therapeutic modalities. We established four MPM cell lines (ACC-MESO-1, ACC-MESO-4, Y-MESO-8A and Y-MESO-8D) from Japanese patients, with the latter two from the same patient with biphasic-like characteristics of MPM, showing epithelial and sarcomatous phenotypes, respectively, in cell culture. These cells grew well in RPMI-1640 medium supplemented with 10% fetal bovine serum under 5% CO2. Mutation and expression analyses demonstrated that the tumor suppressor gene NF2, which is known to be one of the most frequently mutated in MPM, is mutated in ACC-MESO-1. We detected homozygous deletion of p16INK4A/p14ARF in all four MPM cell lines. However, mutations of other tumor suppressor genes, including TP53, and protooncogenes, including KRAS, NRAS, BRAF, EGFR and HER2, were not found in these cell lines. Polymerase chain reaction amplification of the simian virus 40 sequence did not detect any products. We also analyzed genetic alterations of six other MPM cell lines and confirmed frequent mutations of NF2 and p16INK4A/p14ARF. To characterize the biological differences between Y-MESO-8A and Y-MESO-8D, we carried out cDNA microarray analysis and detected genes that were differentially expressed in these two cell lines. Thus, our new MPM cell lines seem to be useful as new models for studying various aspects of the biology of human MPM as well as materials for the development of future therapies.
authors.affiliation: Division of Molecular Oncology, Aichi Cancer Center Research Institute, 1-1 Kanokoden, Chikusa-ku, Nagoya 464-0021, Japan.
authors.forename: Noriyasu
authors.initials: N
authors.lastname: Usami
authors.forename: Takayuki
authors.initials: T
authors.lastname: Fukui
authors.forename: Masashi
authors.initials: M
authors.lastname: Kondo
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Taniguchi
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Yokoyama
authors.forename: Shoichi
authors.initials: S
authors.lastname: Mori
authors.forename: Kohei
authors.initials: K
authors.lastname: Yokoi
authors.forename: Yoshitsugu
authors.initials: Y
authors.lastname: Horio
authors.forename: Kaoru
authors.initials: K
authors.lastname: Shimokata
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Sekido
authors.forename: Toyoaki
authors.initials: T
authors.lastname: Hida
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D000368:Aged; D000818:Animals; D002448:Cell Adhesion; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic / Q000378:metabolism / Q000473:pathology; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics / Q000378:metabolism; D004252:DNA Mutational Analysis; D005260:Female; D016515:Genes, Neurofibromatosis 2; D006801:Humans; D007564:Japan; D008297:Male; D008654:Mesothelioma / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D010997:Pleural Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D017354:Point Mutation; D025803:Tumor Suppressor Protein p14ARF / Q000235:genetics / Q000378:metabolism
chemical_list: D019941:Cyclin-Dependent Kinase Inhibitor p16; D025803:Tumor Suppressor Protein p14ARF