Differential regulation of insulin-like growth factor-I (IGF-I) receptor gene expression by IGF-I and basic fibroblastic growth factor

Catalina Hernández-Sánchez, Haim Werner, Charles T. Roberts, Emily Jane Woo, Dean W. Hum, Stephen M. Rosenthal, Derek LeRoith

    Research output: Contribution to journalArticle

    81 Scopus citations

    Abstract

    Insulin-like growth factor-I receptor (IGF-IR) gene expression is regulated by various stimuli, including hormones, growth factors, and nutritional status. We have investigated the molecular mechanism by which two growth factors, insulin-like growth factor-I (IGF-I) and basic fibroblast growth factor (bFGF) regulate IGF-IR gene expression. bFGF increases the endogenous IGF-IR mRNA levels and IGF-IR promoter activity. This effect is mediated by a region of the IGF-IR promoter located between nucleotides -476 and -188 in the 5'-flanking region. In contrast, IGF-I decreases the IGF-IR mRNA levels. IGF-I down-regulates IGF-IR transcriptional activity as deduced from experiments in which the levels of pre-mRNA and mRNA were measured. IGF- I reduced pre-mRNA and mRNA levels in parallel, while the mRNA stability was found to be unchanged by IGF-I treatment. While these results strongly suggest an effect of IGF-I on IGF-IR transcriptional activity, no specific IGF-I response element was demonstrated in the 5'-untranslated region or 5'- flanking region studied. Thus, bFGF and IGF-I have differential effects on IGF-IR gene transcription, with the IGF-I response region as yet unidentified.

    Original languageEnglish (US)
    Pages (from-to)4663-4670
    Number of pages8
    JournalJournal of Biological Chemistry
    Volume272
    Issue number8
    DOIs
    StatePublished - Feb 21 1997

    ASJC Scopus subject areas

    • Biochemistry
    • Molecular Biology
    • Cell Biology

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