title: A mouse model of KIF5B-RET fusion-dependent lung tumorigenesis.
abstract: Oncogenic fusion of the RET (rearranged during transfection) gene was recently identified as a novel driver gene aberration not only for the development of thyroid carcinoma but also of lung adenocarcinoma, the most frequent histological type of lung cancer. This study constructed and analyzed transgenic mice expressing KIF5B-RET, the predominant form of RET fusion gene specific for lung adenocarcinoma, under the control of the SPC (surfactant protein C) gene promoter. The mice expressed the KIF5B-RET fusion gene specifically in lung alveolar epithelial cells, and developed multiple tumors in the lungs. Treatment of the transgenic mice with vandetanib, which is a RET tyrosine kinase inhibitor approved by the U.S. Food and Drug Administration for the treatment of thyroid carcinoma, for 8 or 20 weeks led to a marked reduction in the number of lung tumors (3.3 versus 0 and 6.5 versus 0.2 per tissue section, respectively; P < 0.01, t-test). The results suggest that the RET fusion functions as a driver for the development of lung tumors, whose growth is inhibited by RET tyrosine kinase inhibitors.
authors: Division of Genome Biology, National Cancer Center Research Institute, Tokyo 104-0045, Japan, Department of Organ Regulatory Surgery, Fukushima Medical University School of Medicine, Fukushima 960-1295, Japan.
authors: Motonobu
authors: M
authors: Saito
authors: Division of Genome Biology, National Cancer Center Research Institute, Tokyo 104-0045, Japan, Department of Organ Regulatory Surgery, Fukushima Medical University School of Medicine, Fukushima 960-1295, Japan.
authors: Teruhide
authors: T
authors: Ishigame
authors: Division of Pathology and Clinical Laboratories, National Cancer Center Hospital, Tokyo, Japan and.
authors: Koji
authors: K
authors: Tsuta
authors: Department of Organ Regulatory Surgery, Fukushima Medical University School of Medicine, Fukushima 960-1295, Japan.
authors: Kensuke
authors: K
authors: Kumamoto
authors: Central Animal Division, National Cancer Center Research Institute, Tokyo 104-0045, Japan.
authors: Toshio
authors: T
authors: Imai
authors: Division of Genome Biology, National Cancer Center Research Institute, Tokyo 104-0045, Japan, tkkohno@ncc.go.jp.
authors: Takashi
authors: T
authors: Kohno
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics*; D000077192:Adenocarcinoma of Lung; D000818:Animals; D063646:Carcinogenesis / Q000235:genetics*; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics*; D051379:Mice; D008822:Mice, Transgenic; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D010880:Piperidines / Q000008:administration & dosage; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage; D011799:Quinazolines / Q000008:administration & dosage
chemical_list: C573239:KIF5B-RET fusion protein, human; D015514:Oncogene Proteins, Fusion; D010880:Piperidines; D047428:Protein Kinase Inhibitors; D011799:Quinazolines; C452423:vandetanib