Regular Article
The IGF-I Receptor in Cancer Research

https://doi.org/10.1006/excr.1999.4667Get rights and content

Abstract

The type 1 insulin-like growth factor receptor (IGF-IR) plays an important role in both normal and abnormal growth. It is particularly important in anchorage-independent growth. Impairment of its function causes apoptosis of tumor cells and inhibition of tumor growth in experimental animals. However, the IGF-IR can also induce differentiation, and eventually cell death, of certain types of cells. Its major substrates, IRS-1 and Shc, determine whether the IGF-IR will transform cells or will cause their differentiation.

References (48)

  • R. Baserga et al.

    IGFs and cell growth

  • C. Sell et al.

    Simian virus 40 large tumor antigen is unable to transform mouse embryonic fibroblasts lacking type-1 IGF receptor

    Proc. Natl. Acad. Sci. USA

    (1993)
  • R. Baserga et al.

    The IGF-I receptor in cell growth, transformation and apoptosis

    Biochim. Biophys. Acta

    (1997)
  • C. Sell et al.

    Effect of a null mutation of the type 1 IGF receptor gene on growth and transformation of mouse embryo fibroblasts

    Mol. Cell. Biol.

    (1994)
  • A. Morrione et al.

    Failure of the bovine papilloma virus to transform mouse embryo fibroblasts with a targeted disruption of the insulin-like growth factor I receptor gene

    J. Virol.

    (1995)
  • M.A. Steller et al.

    Transformation by human papilloma virus 16 E6 and E7: Role of the insulin-like growth factor 1 receptor

    Cancer Res.

    (1996)
  • B. Valentinis et al.

    Insulin-like growth factor 1 receptor signaling in transformation by src oncogene

    Mol. Cell. Biol.

    (1997)
  • D. Coppola et al.

    A functional insulin-like growth factor I receptor is required for the mitogenic and transforming activities of the epidermal growth factor receptor

    Mol. Cell. Biol.

    (1994)
  • T. DeAngelis et al.

    The insulin-like growth factor I receptor is required for the mitogenic and transforming activities of the platelet-derived growth factor receptor

    J. Cell. Physiol.

    (1995)
  • C. D'Ambrosio et al.

    Transforming potential of the insulin receptor substrate 1

    Cell Growth Differ.

    (1995)
  • E. Penuel et al.

    Transformation by v-src: Ras-MAPK and PI3K-mTor mediate parallel pathways

    Mol. Biol. Cell

    (1999)
  • M. Kaleko et al.

    Overexpression of the human insulin-like growth factor 1 receptor promotes ligand-dependent neoplastic transformation

    Mol. Cell. Biol.

    (1990)
  • Z. Pietrzkowski et al.

    Constitutive expression of insulin-like growth factor 1 and insulin-like growth factor 1 receptor abrogates all requirements for exogenous growth factors

    Cell Growth Differ.

    (1992)
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    This work was supported by Grants CA53484 and CA56309 from the National Institutes of Health.

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    Correspondence and reprint requests may be addressed to the author at the above address. Fax: (215) 923-0249. E-mail: [email protected].

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