Targeted Antireceptor Therapy with Monoclonal Antibodies Leads to the Formation of Inactivated Tetrameric Forms of Erbb Receptors.
From: Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine and Abramson Family Cancer Research Institute, 36th Hamilton Walk, Philadelphia, PA 19104, USA.
Journal of immunology (Baltimore, Md. : 1950)
- Publish Date: Jan 2007
- ISSN: 0022-1767
- Volume: 178
- Issue: 2
- Pages: 1021-9
- Medium: Print
- Language: English
- Citation (JAMA): Furuuchi Keiji, Berezov Alan, Kumagai Toru, et al. Targeted Antireceptor Therapy with Monoclonal Antibodies Leads to the Formation of Inactivated Tetrameric Forms of Erbb Receptors.. J. Immunol. Jan 2007;178:1021-9
Abstract
mAbs capable of disabling heterodimeric kinase complexes of the epidermal growth factor receptor (EGFR) and human EGFR type 2/neu have therapeutic relevance to various human cancers. In this study, we demonstrate that in addition to the dimer, EGFR and human EGFR type 2 can associate as homo- and heterotetramers. EGF-induced phosphorylation of the tetramers was significantly lower than that of the dimers, indicating that the tetrameric receptor complexes have impaired signaling activity. Targeting v-erb-b2 erythroblastic leukemia viral oncogene homolog (erbB) receptors with mAbs promoted erbB tetrameric assembly, suggesting that a component of the antitumor activity may be mediated by the ability of Abs to shift the equilibrium from active dimeric to impaired tetrameric receptor complex states. This study suggests a novel therapeutic approach to disable signaling of erbB and potentially other receptors in tumors by biologic agents capable of inducing receptor tetramerization.
Mesh Headings (Keywords): Animals, Antibodies, Monoclonal, Catalysis, Cell Line, Cercopithecus aethiops, Gene Deletion, Humans, Molecular Weight, Protein Binding, Receptor, Epidermal Growth Factor, Receptor, erbB-2
Check for Full Text / PubMed Unique Identifier (PMID): 17202365
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