Insulin-like growth factor binding protein 5 and apoptosis in mammary epithelial cells

Emma Marshman, Kirsty A. Green, David J. Flint, Anne White, Charles H. Streuli, Melissa Westwood

    Research output: Contribution to journalArticlepeer-review

    Abstract

    Insulin-like growth factors (IGFs) are important survival signals that can protect a range of cell types from apoptosis. Although IGF bioavailability is modulated by high affinity interactions with IGF-binding proteins (IGFBPs), there is currently no experimental evidence that IGFBPs regulate the survival function of IGFs in the mammary gland. We have examined IGFBP expression during mammary gland development and studied the effects of IGFBPs on IGF-mediated survival and signalling in mammary epithelial cells in culture. IGFBP-5 protein was greatly increased during days 1-3 of mammary gland involution, when levels of apoptosis are dramatically elevated to remodel the gland after lactation. Primary cultures of mammary epithelial cells (MECs) expressed IGFBP-5 from their basal surface suggesting that IGFBP-5 is suitably located to inhibit IGF signalling. Addition of exogenous IGFBP-5 and IGFBP-3 to MECs suppressed IGF-I-mediated survival, resulting in threefold greater apoptosis in cells incubated with IGF-I and IGFBP-5 compared with IGF-I alone. Examination of signalling pathways involved in apoptosis revealed that phosphorylation of PKB and the forkhead transcription factor, FKHRL1, was induced by IGFs, but that phosphorylation was blocked by IGFBP-5 and IGFBP-3. This study provides evidence that IGFBP-5 plays an important role in the regulation of apoptosis in the mammary gland.
    Original languageEnglish
    Pages (from-to)675-682
    Number of pages7
    JournalJournal of Cell Science
    Volume116
    Issue number4
    DOIs
    Publication statusPublished - 15 Feb 2003

    Keywords

    • Apoptosis
    • Insulin-like growth factor binding proteins
    • Insulin-like growth factors
    • Mammary gland

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