Inhibition of ligand-mediated HER2 activation in androgen-independent prostate cancer.
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.
D000728:Androgens / Q000502:physiology; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D004306:Dose-Response Relationship, Immunologic; D005260:Female; D006801:Humans; D008024:Ligands; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009376:Neoplasms, Hormone-Dependent / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D020890:Neuregulin-1 / Q000494:pharmacology; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000037:antagonists & inhibitors* / Q000276:immunology / Q000378:metabolism; D020893:Receptor, ErbB-3 / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology; D016211:Transforming Growth Factor alpha / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
D000728:Androgens; D000911:Antibodies, Monoclonal; D008024:Ligands; D020890:Neuregulin-1; D018719:Erb-b2 Receptor Tyrosine Kinases; D020893:Receptor, ErbB-3; D011994:Recombinant Proteins; D016211:Transforming Growth Factor alpha