論文

査読有り
2010年4月

Gastric cancer cell line Hs746T harbors a splice site mutation of c-Met causing juxtamembrane domain deletion

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
  • Yoshinari Asaoka
  • ,
  • Motohisa Tada
  • ,
  • Tsuneo Ikenoue
  • ,
  • Motoko Seto
  • ,
  • Mitsuho Imai
  • ,
  • Koji Miyabayashi
  • ,
  • Keisuke Yamamoto
  • ,
  • Shinzo Yamamoto
  • ,
  • Yotaro Kudo
  • ,
  • Dai Mohri
  • ,
  • Yoshihiro Isomura
  • ,
  • Hideaki Ijichi
  • ,
  • Keisuke Tateishi
  • ,
  • Fumihiko Kanai
  • ,
  • Seishi Ogawa
  • ,
  • Masao Omata
  • ,
  • Kazuhiko Koike

394
4
開始ページ
1042
終了ページ
1046
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1016/j.bbrc.2010.03.120
出版者・発行元
ACADEMIC PRESS INC ELSEVIER SCIENCE

Receptor tyrosine kinases (RTKs) are involved in oncogenesis and disease progression for many cancers. Inhibitors targeting them are vigorously developed and some of them are tested in the clinical setting. Amplifications of certain RTKs (c-Met, FGFR2 and ErbB2) have been associated with human gastric cancer progression. According to our genome-wide scans of genetic lesions in 34 gastric cancer cell lines using high-density single-nucleotide polymorphism genotyping microarrays, we confirmed that the c-met locus was amplified in four gastric cancer cell lines (Hs746T, MKN45, NUGC4 and SNU5). It was reported that somatic mutation is occasionally detected in tumor samples of a certain type of cancer with gene amplification. Previous reports showed gastric cancers harbored mutations of FGFR2 and ErbB2, but c-Met oncogenic mutation had not yet been reported. We performed mutational analysis of the cytoplasmic domains of c-Met using the genome DNA of the gastric cancer cell lines, and found that H5746T cells had a splice site mutation of exon 14. By cDNA sequencing and Western blotting, we showed that the mutation caused juxtamembrane domain deletion. Previously, this mutation had been detected only in lung cancer specimens and this deletion resulted in the loss of Cbl E3-ligase binding causing decreased ubiquitination and delayed down-regulation. In conclusion, four gastric cancer cell lines harbored amplification of c-met locus, and among them, H5746T had a putative oncogenic mutation with amplification. This information will be useful for screening of inhibitors targeting gastric cancer with c-Met aberration. (C) 2010 Elsevier Inc. All rights reserved.

Web of Science ® 被引用回数 : 49

リンク情報
DOI
https://doi.org/10.1016/j.bbrc.2010.03.120
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000276986400031&DestApp=WOS_CPL

エクスポート
BibTeX RIS