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

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

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  • Matuzumab and cetuximab activate the epidermal growth factor receptor but fail to trigger downstream signaling by Akt or Erk. Abstract Text:

    takeshi yoshidaTakeshi Yoshida,isamu okamotoIsamu Okamoto,takafumi okabeTakafumi Okabe,tsutomu iwasaTsutomu Iwasa,taroh satohTaroh Satoh,kazuto nishioKazuto Nishio,masahiro fukuokaMasahiro Fukuoka,kazuhiko nakagawaKazuhiko Nakagawa,

    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.

    Matuzumab and cetuximab activate the epidermal growth factor receptor but fail to trigger downstream signaling by Akt or Erk. Publishing Authors By Initials

    t yoshidaT Yoshida,i okamotoI Okamoto,t okabeT Okabe,t iwasaT Iwasa,t satohT Satoh,k nishioK Nishio,m fukuokaM Fukuoka,k nakagawaK Nakagawa,

    For similar abstracts research abstracts see: abstracts research

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

    PUBLICATION TYPE: Journal Article

    Journal: International journal of cancer. Journal internati

    VOLUME: 122

    Page Numbers: 1530-8

    Journal Abbreviation: Int. J. Cancer

    ISSN: 1097-0215

    DAY: 1

    MONTH: Apr

    YEAR: 2008

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

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    LANGUAGE: eng

    NlmUniqueID: 42124

    Matuzumab and cetuximab activate the epidermal growth factor receptor but fail to trigger downstream signaling by Akt or Erk. Keywords Mesh Terms:

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    Grant and Affiliation Information for Matuzumab and cetuximab activate the epidermal growth factor receptor but fail to trigger downstream signaling by Akt or Erk.

    AFFILIATION: Department of Medical Oncology, Kinki University School of Medicine, Osaka, Japan.

    Country: United States

    United States Research PublicationUnited States Research Publication

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    MEDLINETA: Int J Cancer

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