title: Expression of HDAC9 in lung cancer--potential role in lung carcinogenesis.
abstract: Our previous studies identified important molecules involved in lung carcinogenesis through a comprehensive search for the downstream targets of oncogenic KRAS, and these findings suggested that an investigation into the downstream targets of oncogenic KRAS might represent a useful strategy for elucidating the common molecular bases of lung cancer. Among the downstream targets of oncogenic KRAS, a focus was placed on HDAC9, a member of the histone deacetylase family, in the present study because epigenetic modification of DNA or the histone proteins is known to play an important role in carcinogenesis. The immunohistochemical expression of HDAC9 was examined in surgically resected primary lung cancers (130 adenocarcinoma, 49 squamous cell carcinomas, one large cell carcinoma, and 6 small cell carcinomas) and potential associations between its expression level and pathologic factors were analyzed. The results showed that HDAC9 expression levels were lower in lung cancer cells than in non-tumor epithelial cells, and were also significantly lower in adenocarcinomas among the histological types. Moreover, HDAC9 expression levels were significantly lower in adenocarcinomas with lymphatic canal involvement. The restoration of HDAC9 in lung cancer cells losing its expression severely attenuated their growth activity in vitro. These results suggest that HDAC9 may be a suppressor and its downregulation might promote the progression process, especially in lung adenocarcinomas.
authors.affiliation: Department of Pathology, Yokohama City University Graduate School of Medicine 3-9, Future, Kanazawaku, 236-0004, Yokohama, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Okudela
authors.affiliation: Department of Pathology, Yokohama City University Graduate School of Medicine 3-9, Future, Kanazawaku, 236-0004, Yokohama, Japan.
authors.forename: Hideaki
authors.initials: H
authors.lastname: Mitsui
authors.affiliation: Department of Pathology, Yokohama City University Graduate School of Medicine 3-9, Future, Kanazawaku, 236-0004, Yokohama, Japan.
authors.forename: Takehisa
authors.initials: T
authors.lastname: Suzuki
authors.affiliation: Department of Surgery, Yokohama City University Graduate School of Medicine 3-9, Future, Kanazawaku, 236-0004, Yokohama, Japan.
authors.forename: Tetsukan
authors.initials: T
authors.lastname: Woo
authors.affiliation: Department of Pathology, Yokohama City University Graduate School of Medicine 3-9, Future, Kanazawaku, 236-0004, Yokohama, Japan.
authors.forename: Yoko
authors.initials: Y
authors.lastname: Tateishi
authors.affiliation: Department of Pathology, Yokohama City University Graduate School of Medicine 3-9, Future, Kanazawaku, 236-0004, Yokohama, Japan.
authors.forename: Shigeaki
authors.initials: S
authors.lastname: Umeda
authors.affiliation: Department of Pathology, Yokohama City University Graduate School of Medicine 3-9, Future, Kanazawaku, 236-0004, Yokohama, Japan.
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Saito
authors.affiliation: Division of General Thoracic Surgery, Kanagawa Prefectural Cardiovascular and Respiratory Center Hospital 6-16-1, Tomioka-higashi, Kanazawa-ku, 230-0051, Yokohama, Japan.
authors.forename: Michihiko
authors.initials: M
authors.lastname: Tajiri
authors.affiliation: Department of Surgery, Yokohama City University Graduate School of Medicine 3-9, Future, Kanazawaku, 236-0004, Yokohama, Japan.
authors.forename: Munetaka
authors.initials: M
authors.lastname: Masuda
authors.affiliation: Department of Pathology, Yokohama City University Graduate School of Medicine 3-9, Future, Kanazawaku, 236-0004, Yokohama, Japan.
authors.forename: Kenichi
authors.initials: K
authors.lastname: Ohashi
mesh_terms: D015153:Blotting, Western; D063646:Carcinogenesis / Q000378:metabolism; D002277:Carcinoma / Q000378:metabolism* / Q000473:pathology*; D045744:Cell Line, Tumor; D018450:Disease Progression; D015536:Down-Regulation; D006655:Histone Deacetylases / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000378:metabolism* / Q000473:pathology*; D016133:Polymerase Chain Reaction; D012097:Repressor Proteins / Q000378:metabolism*; D014162:Transfection
chemical_list: D012097:Repressor Proteins; C486544:HDAC9 protein, human; D006655:Histone Deacetylases
keywords: HDAC9; KRAS; lung cancer