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ID 110044
Title Alternative
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
Author
Kohmoto, Tomohiro Tokushima University
Watanabe, Miki Tokushima University
Keywords
TRIM58
early-stage lung adenocarcinoma
tumor suppressor gene
methylation
smoking status
Content Type
Thesis or Dissertation
Description
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.
Journal Title
Oncotarget
ISSN
19492553
Publisher
Impact Journals
Volume
8
Issue
2
Start Page
2890
End Page
2905
Published Date
2016-12-01
Remark
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
Rights
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
DOI (Published Version)
URL ( Publisher's Version )
FullText File
language
eng
TextVersion
ETD
MEXT report number
甲第3024号
Diploma Number
甲医第1328号
Granted Date
2017-03-21
Degree Name
Doctor of Medical Science
Grantor
Tokushima University
departments
Medical Sciences
University Hospital