Abstract
Hormone-independent tumor growth and metastasis are associated with increased mortality in human prostate cancer. In this study, we evaluate a potential role for ligand-mediated activation of HER2 receptor tyrosine kinase in androgen-independent prostate cancers. HER2, HER3, and epidermal growth factor receptor were detected in the androgen-independent cell line 22Rv1. Heregulin stimulation results in receptor phosphorylation and cell proliferation that is inhibited by increasing concentrations of anti-HER2 recombinant humanized monoclonal antibody (rhuMAb) 2C4. Furthermore, inhibition of tumor growth was observed in xenografts derived from 22Rv1 cells when treated with rhuMAb 2C4 in a dose-dependent manner. These studies provide a framework, both in vitro and in vivo, to examine the molecular mechanisms of ligand-driven HER2 activation in androgen-independent tumorigenesis.
MeSH terms
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Androgens / physiology
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Animals
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Antibodies, Monoclonal / pharmacology*
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Cell Division / drug effects
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Dose-Response Relationship, Immunologic
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Female
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Humans
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Ligands
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Male
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Mice
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Mice, Inbred BALB C
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Mice, Nude
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Neoplasms, Hormone-Dependent / metabolism
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Neoplasms, Hormone-Dependent / pathology
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Neoplasms, Hormone-Dependent / therapy
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Neuregulin-1 / pharmacology
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Prostatic Neoplasms / metabolism
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Prostatic Neoplasms / pathology
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Prostatic Neoplasms / therapy*
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Receptor, ErbB-2 / antagonists & inhibitors*
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Receptor, ErbB-2 / immunology
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Receptor, ErbB-2 / metabolism
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Receptor, ErbB-3 / metabolism
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Recombinant Proteins / pharmacology
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Transforming Growth Factor alpha / pharmacology
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Tumor Cells, Cultured
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Xenograft Model Antitumor Assays
Substances
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Androgens
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Antibodies, Monoclonal
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Ligands
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Neuregulin-1
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Recombinant Proteins
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Transforming Growth Factor alpha
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Receptor, ErbB-2
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Receptor, ErbB-3