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ID 110044
タイトル別表記
早期肺腺癌において癌抑制遺伝子TRIM 58はプロモーター領域のメチル化により高頻度に抑制される
著者
梶浦, 耕一郎 徳島大学大学院医科学教育部(医学専攻) KAKEN研究者をさがす
Kohmoto, Tomohiro Tokushima University
Watanabe, Miki Tokushima University
キーワード
TRIM58
early-stage lung adenocarcinoma
tumor suppressor gene
methylation
smoking status
資料タイプ
学位論文
抄録
In this study, we aimed to identify novel drivers that would be epigenetically altered through aberrant methylation in early-stage lung adenocarcinoma (LADC), regardless of the presence or absence of tobacco smoking-induced epigenetic field defects. Through genome-wide screening for aberrantly methylated CpG islands (CGIs) in 12 clinically uniform, stage-I LADC cases affecting six non-smokers and six smokers, we identified candidate tumor-suppressor genes (TSGs) inactivated by hypermethylation. Through systematic expression analyses of those candidates in panels of additional tumor samples and cell lines treated or not treated with 5-aza-deoxycitidine followed by validation analyses of cancer-specific silencing by CGI hypermethylation using a public database, we identified TRIM58 as the most prominent candidate for TSG. TRIM58 was robustly silenced by hypermethylation even in early-stage primary LADC, and the restoration of TRIM58 expression in LADC cell lines inhibited cell growth in vitro and in vivo in anchorage-dependent and -independent manners. Our findings suggest that aberrant inactivation of TRIM58 consequent to CGI hypermethylation might stimulate the early carcinogenesis of LADC regardless of smoking status; furthermore, TRIM58 methylation might be a possible early diagnostic and epigenetic therapeutic target in LADC.
掲載誌名
Oncotarget
ISSN
19492553
出版者
Impact Journals
8
2
開始ページ
2890
終了ページ
2905
発行日
2016-12-01
備考
内容要旨・審査要旨・論文本文の公開:
内容要旨・審査要旨:LID201704141005.pdf
論文本文:LID201704141006.pdf
本論文は, 著者Koichiro Kajiuraの学位論文として提出され, 学位審査・授与の対象となっている。
P.2890著者の英語表記に誤植(誤)Miki Watabnabe(正)Miki Watanabe
権利情報
Copyright: © 2017 Kajiura et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
EDB ID
出版社版DOI
出版社版URL
フルテキストファイル
言語
eng
著者版フラグ
博士論文全文を含む
文科省報告番号
甲第3024号
学位記番号
甲医第1328号
学位授与年月日
2017-03-21
学位名
博士(医学)
学位授与機関
徳島大学
部局
医学系
病院