MISC

2007年9月

Pertuzumab, a novel HER dimerization inhibitor, inhibits the growth of human lung cancer cells mediated by the HER3 signaling pathway

CANCER SCIENCE
  • Kazuko Sakai
  • ,
  • Hideyuki Yokote
  • ,
  • Kimiko Murakami-Murofushi
  • ,
  • Tomohide Tamura
  • ,
  • Nagahiro Saijo
  • ,
  • Kazuto Nishio

98
9
開始ページ
1498
終了ページ
1503
記述言語
英語
掲載種別
DOI
10.1111/j.1349-7006.2007.005853.x
出版者・発行元
BLACKWELL PUBLISHING

A humanized anti-HER2 monoclonal antibody pertuzumab (Omnitarg, 2C4), binding to a different HER2 epitope than trastuzumab, is known as an inhibitor of heterodimerization of the HER receptors. Potent antitumor activity against HER2-expressing breast and prostate cancer cell lines has been clarified, but this potential is not clear against lung cancers. The authors investigated the in vitro anti-tumor activity of pertuzumab against eight non-small cell lung cancer cells expressing various members of the HER receptors. A lung cancer 11_18 cell line expressed a large amount of HER2 and HER3, and its cell growth was stimulated by an HER3 ligand, heregulin (HRG)-alpha. Pertuzumab significantly inhibited the HRG-alpha-stimulated cellular growth of the 11_18 cells. Pertuzumab blocked HRG-alpha-stimulated phosphorylation of HER3, mitogen-activated protein kinase (MAPK), and Akt. In contrast, pertuzumab failed to block epidermal growth factor (EGF)-stimulated phosphorylation of EGF receptor (EGFR) and MAPK. Immunoprecipitation showed that pertuzumab inhibited HRG-alpha-stimulated HER2/HER3 heterodimer formation. HRG-alpha-stimulated HER3 phosphorylation was also observed in the PC-9 cells co-overexpressing EGFR, HER2, and HER3, but the cell growth was neither stimulated by HRG-alpha nor inhibited by pertuzumab. The present results suggest that pertuzumab is effective against HRG-alpha-dependent cell growth in lung cancer cells through inhibition of HRG-alpha-stimulated HER2/HER3 signaling.

Web of Science ® 被引用回数 : 65

リンク情報
DOI
https://doi.org/10.1111/j.1349-7006.2007.005853.x
CiNii Articles
http://ci.nii.ac.jp/naid/10019999142
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/17627612
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000248968500032&DestApp=WOS_CPL

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