Matuzumab and cetuximab activate the epidermal growth factor receptor but fail to trigger downstream signaling by Akt or Erk

Takeshi Yoshida, Isamu Okamoto, Takafumi Okabe, Tsutomu Iwasa, Taroh Satoh, Kazuto Nishio, Masahiro Fukuoka, Kazuhiko Nakagawa

研究成果: ジャーナルへの寄稿記事

40 引用 (Scopus)

抄録

Molecular inhibition of the epidermal growth factor receptor (EGFR) is a promising anticancer strategy, and monoclonal antibodies (mAbs) to EGFR are undergoing extensive evaluation in preclinical and clinical trials. However, the effects of anti-EGFR mAbs on EGFR signaling have remained unclear. We have now examined the effects of 2 anti-EGFR mAbs, matuzumab (EMD72000) and cetuximab (Erbitux), both of which are currently under assessment for treatment of various cancers, on EGFR signal transduction and cell survival in nonsmall cell lung cancer cell lines. Similar to EGF, matuzumab and cetuximab each induced phosphorylation of EGFR at several tyrosine phosphorylation sites as a result of receptor dimerization and activation of the receptor tyrosine kinase. In contrast to the effects of EGF, however, EGFR activation induced by these antibodies was not accompanied by receptor turnover or by activation of downstream signaling pathways that are mediated by Akt and Erk and are important for regulation of cell proliferation and survival. In addition, clonogenic survival assays revealed that matuzumab and cetuximab reduced the survival rate of H292 cells, in which they also inhibited the EGF-induced activation of Akt and Erk. Although we have examined only a few cell lines, our results indicate that the antitumor effects of matuzumab and cetuximab depend on inhibition of EGFR downstream signaling mediated by Akt or Erk rather than on inhibition of EGFR itself.

元の言語英語
ページ(範囲)1530-1538
ページ数9
ジャーナルInternational Journal of Cancer
122
発行部数7
DOI
出版物ステータス出版済み - 4 1 2008

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Epidermal Growth Factor Receptor
Epidermal Growth Factor
Monoclonal Antibodies
Cell Survival
Phosphorylation
Cetuximab
matuzumab
Cell Line
Receptor Protein-Tyrosine Kinases
Dimerization
Non-Small Cell Lung Carcinoma
Tyrosine
Signal Transduction
Cell Proliferation
Clinical Trials
Antibodies

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

これを引用

Matuzumab and cetuximab activate the epidermal growth factor receptor but fail to trigger downstream signaling by Akt or Erk. / Yoshida, Takeshi; Okamoto, Isamu; Okabe, Takafumi; Iwasa, Tsutomu; Satoh, Taroh; Nishio, Kazuto; Fukuoka, Masahiro; Nakagawa, Kazuhiko.

:: International Journal of Cancer, 巻 122, 番号 7, 01.04.2008, p. 1530-1538.

研究成果: ジャーナルへの寄稿記事

Yoshida, Takeshi ; Okamoto, Isamu ; Okabe, Takafumi ; Iwasa, Tsutomu ; Satoh, Taroh ; Nishio, Kazuto ; Fukuoka, Masahiro ; Nakagawa, Kazuhiko. / Matuzumab and cetuximab activate the epidermal growth factor receptor but fail to trigger downstream signaling by Akt or Erk. :: International Journal of Cancer. 2008 ; 巻 122, 番号 7. pp. 1530-1538.
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AU - Satoh, Taroh

AU - Nishio, Kazuto

AU - Fukuoka, Masahiro

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