Cancer Science. Volume 97 Page 387 – May 2006. [Link]
Noriyasu Usami1,2, Takayuki Fukui1,2, Masashi Kondo3, Tetsuo Taniguchi1,2, Toshihiko Yokoyama1,3, Shoichi Mori4, Kohei Yokoi2, Yoshitsugu Horio5, Kaoru Shimokata3, Yoshitaka Sekido1,6 and Toyoaki Hida5
1Division of Molecular Oncology, Aichi Cancer Center Research Institute, 1-1 Kanokoden, Chikusa-ku, Nagoya 464-0021;
2Division of General Thoracic Surgery, Nagoya University School of Medicine;
3Department of Respiratory Medicine, Nagoya University School of Medicine, Nagoya 466-8550;
4Department of Thoracic Surgery, Aichi Cancer Center Hospital, and
5Department of Thoracic Oncology, Aichi Cancer Center Hospital, Chikusa-ku, Nagoya 464-0021, Japan
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.