The IGFI receptor gene: A molecular target for disrupted transcription factors

Haim Werner, Charles Roberts

    Research output: Contribution to journalArticle

    58 Citations (Scopus)

    Abstract

    The biological actions of the insulin-like growth factors, IGFI and IGFII, are mediated by their activation of the IGFI receptor (IGFIR), a transmembrane heterotetramer linked to the RAS-RAF-MAPK and PI3K-PKB/AKT signal transduction cascades. The IGFIR displays potent mitogenic, antiapoptotic, and transforming activities, and is a prerequisite for oncogenic transformation. A number of transcription factors have been identified that control the expression of this gene and therefore determine, to a significant extent, the proliferative status of the cell. The purpose of this review is to summarize data showing that, under normal physiological conditions, expression of the IGFIR is under inhibitory control by a family of negative growth regulators or tumor suppressors. Cells with a reduced number of cell-surface receptors are unable to progress through the cell cycle and remain in a postmitotic state. Loss-of-function mutation of tumor suppressors in certain cancers results in transcriptional derepression of the IGFIR gene, with ensuing increases in the levels of IGFIR and increased proliferative capacity. Understanding the molecular mechanisms responsible for transcriptional regulation of the IGFIR gene will prove important in designing novel therapies aimed at targeting the IGF axis.

    Original languageEnglish (US)
    Pages (from-to)113-120
    Number of pages8
    JournalGenes Chromosomes and Cancer
    Volume36
    Issue number2
    DOIs
    StatePublished - Feb 1 2003

    Fingerprint

    Transcription Factors
    Genetic Suppression
    Genes
    Neoplasms
    Cell Surface Receptors
    Somatomedins
    Phosphatidylinositol 3-Kinases
    Signal Transduction
    Cell Cycle
    Gene Expression
    Growth
    Therapeutics

    ASJC Scopus subject areas

    • Cancer Research
    • Genetics

    Cite this

    The IGFI receptor gene : A molecular target for disrupted transcription factors. / Werner, Haim; Roberts, Charles.

    In: Genes Chromosomes and Cancer, Vol. 36, No. 2, 01.02.2003, p. 113-120.

    Research output: Contribution to journalArticle

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