Anti-HER-3 MAbs inhibit HER-3-mediated signaling in breast cancer cell lines resistant to anti-HER-2 antibodies

✍ Scribed by Edward Htun van der Horst; Marta Murgia; Martin Treder; Axel Ullrich

• Book ID: 102270607
• Publisher: John Wiley and Sons
• Year: 2005
• Tongue: French
• Weight: 386 KB
• Volume: 115
• Category: Article
• ISSN: 0020-7136
• DOI: 10.1002/ijc.20867

✦ Synopsis

Abstract

Two members of the EGF receptor family, HER2 and HER3, act as key oncogenes in breast cancer cells. A MAb against HER2, trastuzumab, interferes with HER2 signaling and istherapeutically effective in humans. Here, we explored the biologic effects of an antibody against HER3 (α‐HER3^ECD^) in the invasive breast cancer cell lines MCF‐7^ADR^ and MDA‐MB‐468. Pretreating the breast cancer cells with α‐HER3^ECD^ prior to Heregulin stimulation caused significant reduction of the migratory and proliferative properties. This reduction is due to a substantial decrease in the tyrosine phosphorylation content of HER2 and to a modification of the HER2/HER3 association, which ultimately inhibits the activity of the downstream effectors phosphatidyinositol‐3‐OH‐kinase and c‐jun‐terminal kinase. Furthermore, HER3 is internalized and not activated by HRG after pretreatment with α‐HER3^ECD^. Our data reinforce the notion that HER3 could be a key target in cancer drug design and show the great potential of anti‐HER3 antibodies for the therapy of breast cancer and other malignancies characterized by overexpression of HER3. © 2005 Wiley‐Liss, Inc.