title: A new human lung adenocarcinoma cell line harboring the EML4-ALK fusion gene.
abstract: OBJECTIVE
  The echinoderm microtubule associated protein-like 4 (EML4)-anaplastic lymphoma kinase (ALK) fusion gene was identified in patients with non-small cell lung cancer. To the best of our knowledge, there are only three cell lines harboring the EML4-ALK fusion gene, which have contributed to the development of therapeutic strategies. Therefore, we tried to establish a new lung cancer cell line harboring EML4-ALK.
  
  
  METHODS
  A 61-year-old Japanese female presented with chest discomfort. She was diagnosed with left lung adenocarcinoma with T4N3M1 Stage IV. Although she was treated with chemotherapy, her disease progressed with massive pleural effusion. Because the EML4-ALK rearrangement was found in a biopsied specimen using fluorescence in situ hybridization, she was treated with crizotinib. She did well for 3 months.
  
  
  RESULTS
  Tumor cells were obtained from the malignant pleural effusion before treatment with crizotinib. Cells continued to proliferate substantially for several weeks. The cell line was designated ABC-11. The EML4-ALK fusion protein and genes were identified in ABC-11 cells using fluorescence in situ hybridization and immunohistochemistry, respectively. ABC-11 cells were sensitive to crizotinib and next-generation ALK inhibitors (ceritinib and AP26113), as determined by a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Phosphorylated ALK protein and its downstream signaling were suppressed by treatment with crizotinib in western blotting. Furthermore, we could transplant ABC-11 cells subcutaneously into BALB/c nu/nu mice.
  
  
  CONCLUSIONS
  We successfully established a new lung adenocarcinoma cell line harboring the EML4-ALK fusion gene. This cell line could contribute to future research of EML4-ALK-positive lung cancer both in vivo and in vitro.
authors.affiliation: Department of Clinical Pharmaceutics, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences and Okayama University Hospital, Okayama.
authors.forename: Hideko
authors.initials: H
authors.lastname: Isozaki
authors.affiliation: Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences and Okayama University Hospital, Okayama.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Yasugi
authors.affiliation: Department of General Internal Medicine 4, Kawasaki Hospital, Kawasaki Medical School, Okayama.
authors.forename: Nagio
authors.initials: N
authors.lastname: Takigawa
authors.affiliation: Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences and Okayama University Hospital, Okayama.
authors.forename: Katsuyuki
authors.initials: K
authors.lastname: Hotta
authors.affiliation: Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences and Okayama University Hospital, Okayama.
authors.forename: Eiki
authors.initials: E
authors.lastname: Ichihara
authors.affiliation: Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences and Okayama University Hospital, Okayama.
authors.forename: Akihiko
authors.initials: A
authors.lastname: Taniguchi
authors.affiliation: Department of Thoracic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama.
authors.forename: Shinichi
authors.initials: S
authors.lastname: Toyooka
authors.affiliation: Department of Thoracic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama.
authors.forename: Shinsuke
authors.initials: S
authors.lastname: Hashida
authors.affiliation: Department of Clinical Pharmaceutics, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences and Okayama University Hospital, Okayama.
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Sendo
authors.affiliation: Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences and Okayama University Hospital, Okayama.
authors.forename: Mitsune
authors.initials: M
authors.lastname: Tanimoto
authors.affiliation: Department of Allergy and Respiratory Medicine (Thoracic Oncology), Okayama University Hospital, Okayama, Japan kkiura@md.okayama-u.ac.jp.
authors.forename: Katsuyuki
authors.initials: K
authors.lastname: Kiura
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000235:genetics; D000077192:Adenocarcinoma of Lung; D000077548:Anaplastic Lymphoma Kinase; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D018797:Cell Cycle Proteins / Q000235:genetics*; D045744:Cell Line, Tumor; D000077547:Crizotinib; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D008175:Lung Neoplasms / Q000188:drug therapy / Q000235:genetics; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008869:Microtubule-Associated Proteins / Q000235:genetics*; D008875:Middle Aged; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D016066:Pleural Effusion, Malignant / Q000188:drug therapy / Q000235:genetics; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D011720:Pyrazoles / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D011743:Pyrimidines / Q000494:pharmacology; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics*; D012697:Serine Endopeptidases / Q000235:genetics*; D015398:Signal Transduction / Q000187:drug effects; D013450:Sulfones / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D018797:Cell Cycle Proteins; D008869:Microtubule-Associated Proteins; D015514:Oncogene Proteins, Fusion; D047428:Protein Kinase Inhibitors; D011720:Pyrazoles; D011725:Pyridines; D011743:Pyrimidines; D013450:Sulfones; D000077547:Crizotinib; C000626173:ALK protein, human; C000626174:Alk protein, mouse; D000077548:Anaplastic Lymphoma Kinase; D020794:Receptor Protein-Tyrosine Kinases; C415585:EML4 protein, human; D012697:Serine Endopeptidases; C586847:ceritinib
keywords: EML4-ALK; crizotinib; lung cancer