title: A monoclonal antibody to the human HER3 receptor inhibits Neuregulin 1-beta binding and co-operates with Herceptin in inhibiting the growth of breast cancer derived cell lines.
abstract: The HER3 protein contributes to malignant transformation in breast and other cancer types as a consequence of elevated levels of expression, particularly in the presence of the HER2 protein. We show here that an antibody, called SGP1, to the extracellular domain of the HER3 receptor can inhibit completely Neuregulin stimulated growth of cultured breast cancer cells. Herceptin is a humanised monoclonal antibody to the HER2 protein which has an established role in the treatment of some patients with breast cancer. We demonstrate that Herceptin and SGP1 can bind simultaneously to breast cancer cells expressing both the HER2 and HER3 proteins. In the presence of moderate levels of Herceptin, addition of the SGP1 monoclonal antibody gave a dose-dependent inhibition of the growth of cells expressing both the high levels and moderate levels of HER2. The combination of Herceptin with SGP1 is effective in inhibiting breast cancer cell growth in cases where both HER2 and HER3 are expressed.
authors.affiliation: Cancer Biology Laboratory, Microscopy and Imaging Facility, School of Biosciences, University of Kent, Canterbury, Kent, CT2 7NJ, UK.
authors.forename: Edith
authors.initials: E
authors.lastname: Blackburn
authors.forename: Stefania
authors.initials: S
authors.lastname: Zona
authors.forename: Mariana L
authors.initials: ML
authors.lastname: Murphy
authors.forename: Ian R
authors.initials: IR
authors.lastname: Brown
authors.forename: Samuel K W
authors.initials: SK
authors.lastname: Chan
authors.forename: William J
authors.initials: WJ
authors.lastname: Gullick
mesh_terms: D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D061067:Antibodies, Monoclonal, Humanized / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001667:Binding, Competitive; D001943:Breast Neoplasms / Q000188:drug therapy*; D045744:Cell Line, Tumor / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects*; D004354:Drug Screening Assays, Antitumor; D004357:Drug Synergism; D005260:Female; D006801:Humans; D020890:Neuregulin-1 / Q000378:metabolism* / Q000502:physiology; D011485:Protein Binding; D020893:Receptor, ErbB-3 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000068878:Trastuzumab
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D020890:Neuregulin-1; C117467:neuregulin beta; D020893:Receptor, ErbB-3; D000068878:Trastuzumab