1. Targeting ligand-activated ErbB2 signaling inhibits breast and prostate tumor growth.
- Author
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Agus DB, Akita RW, Fox WD, Lewis GD, Higgins B, Pisacane PI, Lofgren JA, Tindell C, Evans DP, Maiese K, Scher HI, and Sliwkowski MX
- Subjects
- Androgens metabolism, Animals, Antibodies, Monoclonal immunology, Antineoplastic Agents pharmacology, Antineoplastic Agents therapeutic use, Breast Neoplasms metabolism, Cell Division drug effects, Female, Gene Expression Regulation, Neoplastic, Humans, Ligands, Male, Mice, Neoplasm Transplantation, Neuregulin-1 pharmacology, Prostatic Neoplasms metabolism, Protein Binding drug effects, RNA, Messenger genetics, RNA, Messenger metabolism, Receptor, ErbB-2 genetics, Receptor, ErbB-2 immunology, Receptor, ErbB-2 metabolism, Receptor, ErbB-3 metabolism, Time Factors, Transplantation, Heterologous, Tumor Cells, Cultured, Antibodies, Monoclonal therapeutic use, Breast Neoplasms drug therapy, Breast Neoplasms pathology, Prostatic Neoplasms drug therapy, Prostatic Neoplasms pathology, Receptor, ErbB-2 antagonists & inhibitors, Signal Transduction drug effects
- Abstract
ErbB2 is a ligand-less member of the ErbB receptor family that functions as a coreceptor with EGFR, ErbB3, and ErbB4. Here, we describe an approach to target ErbB2's role as a coreceptor using a monoclonal antibody, 2C4, which sterically hinders ErbB2's recruitment into ErbB ligand complexes. Inhibition of ligand-dependent ErbB2 signaling by 2C4 occurs in both low- and high-ErbB2-expressing systems. Since the ErbB3 receptor contains an inactive tyrosine kinase domain, 2C4 is very effective in blocking heregulin-mediated ErbB3-ErbB2 signaling. We demonstrate that the in vitro and in vivo growth of several breast and prostate tumor models is inhibited by 2C4 treatment.
- Published
- 2002
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