title: Proteome analysis for downstream targets of oncogenic KRAS--the potential participation of CLIC4 in carcinogenesis in the lung.
abstract: This study investigated the proteome modulated by oncogenic KRAS in immortalized airway epithelial cells. Chloride intracellular channel protein 4 (CLIC4), S100 proteins (S100A2 and S100A11), tropomyosin 2, cathepsin L1, integrinsα3, eukaryotic elongation factor 1, vimentin, and others were discriminated. We here focused on CLIC4 to investigate its potential involvement in carcinogenesis in the lung because previous studies suggested that some chloride channels and chloride channel regulators could function as tumor suppressors. CILC4 protein levels were reduced in some lung cancer cell lines. The restoration of CLIC4 in lung cancer cell lines in which CLIC4 expression was reduced attenuated their growth activity. The immunohistochemical expression of the CLIC4 protein was weaker in primary lung cancer cells than in non-tumorous airway epithelial cells and was occasionally undetectable in some tumors. CLIC4 protein levels were significantly lower in a subtype of mucinous ADC than in others, and were also significantly lower in KRAS-mutated ADC than in EGFR-mutated ADC. These results suggest that the alteration in CLIC4 could be involved in restrictedly the development of a specific fraction of lung adenocarcinomas. The potential benefit of the proteome modulated by oncogenic KRAS to lung cancer research has been demonstrated.
authors: Department of Pathology, Yokohama City University Graduate School of Medicine, 3-9, Future, Kanazawa-ku, Yokohama, Japan.
authors: Koji
authors: K
authors: Okudela
authors: Department of Biochemistry/Cell Biology, Nippon Medical University, 1-1-5, Sendagi, Bunkyo-ku, Tokyo, Japan.
authors: Akira
authors: A
authors: Katayama
authors: Department of Surgey, Yokohama City University Graduate School of Medicine, 3-9, Future, Kanazawa-ku, Yokohama, Japan.
authors: Tetsukan
authors: T
authors: Woo
authors: Department of Pathology, Yokohama City University Graduate School of Medicine, 3-9, Future, Kanazawa-ku, Yokohama, Japan.
authors: Hideaki
authors: H
authors: Mitsui
authors: Department of Pathology, Yokohama City University Graduate School of Medicine, 3-9, Future, Kanazawa-ku, Yokohama, Japan.
authors: Takehisa
authors: T
authors: Suzuki
authors: Department of Pathology, Yokohama City University Graduate School of Medicine, 3-9, Future, Kanazawa-ku, Yokohama, Japan.
authors: Yoko
authors: Y
authors: Tateishi
authors: Department of Pathology, Yokohama City University Graduate School of Medicine, 3-9, Future, Kanazawa-ku, Yokohama, Japan.
authors: Shigeaki
authors: S
authors: Umeda
authors: Division of General Thoracic Surgery, Kanagawa Prefectural Cardiovascular and Respiratory Center Hospital, 6-16-1, Tomioka-higashi, Kanazawa-ku, Yokohama, Japan.
authors: Michihiko
authors: M
authors: Tajiri
authors: Department of Surgey, Yokohama City University Graduate School of Medicine, 3-9, Future, Kanazawa-ku, Yokohama, Japan.
authors: Munetaka
authors: M
authors: Masuda
authors: Department of Enviromental Medicine, Nippon Medical University, 1-1-5, Sendagi, Bunkyo-ku, Tokyo, Japan.
authors: Noriyuki
authors: N
authors: Nagahara
authors: Department of Pathology, Yokohama City University Graduate School of Medicine, 3-9, Future, Kanazawa-ku, Yokohama, Japan.
authors: Hitoshi
authors: H
authors: Kitamura
authors: Department of Pathology, Yokohama City University Graduate School of Medicine, 3-9, Future, Kanazawa-ku, Yokohama, Japan.
authors: Kenichi
authors: K
authors: Ohashi
mesh_terms: D063646:Carcinogenesis / Q000378:metabolism* / Q000473:pathology; D002457:Cell Extracts; D045744:Cell Line, Tumor; D018118:Chloride Channels / Q000378:metabolism*; D018572:Disease-Free Survival; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism* / Q000473:pathology; D035683:MicroRNAs / Q000378:metabolism; D020543:Proteome / Q000378:metabolism*; D040901:Proteomics; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D016283:Proto-Oncogene Proteins p21(ras); D034741:RNA, Small Interfering / Q000378:metabolism; D014161:Transduction, Genetic; D018631:ras Proteins / Q000235:genetics*
chemical_list: C464459:CLIC4 protein, human; D002457:Cell Extracts; D018118:Chloride Channels; C117307:KRAS protein, human; C534612:MIRN31 microRNA, human; D035683:MicroRNAs; D020543:Proteome; D011518:Proto-Oncogene Proteins; D034741:RNA, Small Interfering; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins