Expression of epidermal growth factor receptor or ErbB3 facilitates geldanamycin-induced down-regulation of ErbB2

Nina Marie Pedersen, Kamilla Breen, Marianne Skeie Rødland, Camilla Haslekås, Espen Stang, Inger Helene Madshus

    Research output: Contribution to journalArticle

    16 Scopus citations

    Abstract

    Overexpression of the epidermal growth factor receptor (EGFR), ErbB2, and ErbB3 promotes growth and anti- apoptotic signaling. Overexpression of ErbB2 in breast cancer is associated with poor clinical outcome, and ways of down-regulating ErbB2 are important as therapeutic approaches. In contrast to EGFR, ErbB2 has been shown to be endocytosis deficient. However, down-regulation of ErbB2 can be induced by incubation of cells with geldanamycin and geldanamycin derivatives, counteracting the stabilizing function of heat shock protein 90 on ErbB2. In the present study, we have made use of stably transfected isogenic cell lines expressing ErbB2 only or ErbB2 together with EGFR and/or ErbB3. We now show that whereas ErbB2 can be down-regulated by incubation with geldanamycin in cells expressing ErbB2 only, the rate of geldanamycin- induced down-regulation increases significantly when the cells additionally express EGFR and/or ErbB3. This increase does, however, not correlate with activation/ phosphorylation of ErbB2. The potential of heterodimer formation in ErbB2-positive breast cancer cells could thus turn out to be prognostically predictive with respect to outcome of treatment with geldanamycin derivatives.

    Original languageEnglish (US)
    Pages (from-to)275-284
    Number of pages10
    JournalMolecular Cancer Research
    Volume7
    Issue number2
    DOIs
    StatePublished - Feb 1 2009

    ASJC Scopus subject areas

    • Molecular Biology
    • Oncology
    • Cancer Research

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