論文

査読有り
2017年8月

Correlation between histone acetylation and expression of Notch1 in human lung carcinoma and its possible role in combined small-cell lung carcinoma

LABORATORY INVESTIGATION
  • Wael Abdo Hassan
  • ,
  • Shin-Ichiro Takebayashi
  • ,
  • Mohamed Osama Ali Abdalla
  • ,
  • Kosuke Fujino
  • ,
  • Shinji Kudoh
  • ,
  • Yamoto Motooka
  • ,
  • Yonosuke Sato
  • ,
  • Yoshiki Naito
  • ,
  • Koichi Higaki
  • ,
  • Joeji Wakimoto
  • ,
  • Seiji Okada
  • ,
  • Mituyoshi Nakao
  • ,
  • Yuichi Ishikawa
  • ,
  • Takaaki Ito

97
8
開始ページ
913
終了ページ
921
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1038/labinvest.2017.36
出版者・発行元
NATURE PUBLISHING GROUP

Combined small-cell lung carcinoma (cSCLC) is composed of small-cell lung carcinoma (SCLC) admixed with non-small-cell lung carcinoma (NSCLC). Evaluating the molecular differences between SCLC and NSCLC could lead to a better understanding of the pathogenesis of such neoplasms. Therefore, in this study, we investigated the correlation between histone acetylation and Notch1 expression in lung carcinoma. Using chromatin immunoprecipitation (ChIP) assay, we measured the level of acetylated histone H3 around the promoter region of Notch1 in SCLC and NSCLC cells. We then treated SCLC cells with trichostatin A (TSA) and characterized the level of histone H3 acetylation at Notch1. In addition, TSA-treated cells were injected into immune-compromised mice, for analysis of the ex vivo tumor xenograft phenotype. The level of acetylated histone H3 surrounding the Notch1 promoter was lower in lung cancer cells not expressing Notch1. Tumors originated from TSA-treated SCLC cells occasionally formed an epithelial-like glandular arrangement of cells; with Notch1 expression and decreased expression of neuroendocrine (NE) markers. Histone deacetylation around the promoter region of Notch1 inhibits Notch1 protein expression in SCLC and the restoration of Notch1 expression in SCLC leads to the concurrent appearance of epithelial-like areas within the SCLC, which could provide a possible mechanism for histogenesis of cSCLC.

Web of Science ® 被引用回数 : 8

リンク情報
DOI
https://doi.org/10.1038/labinvest.2017.36
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000406399500003&DestApp=WOS_CPL
ID情報
  • DOI : 10.1038/labinvest.2017.36
  • ISSN : 0023-6837
  • eISSN : 1530-0307
  • Web of Science ID : WOS:000406399500003

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