Role of the IGF-I receptor in mutagenesis and tumor promotion

• Published in: Journal of endocrinology Vol. 152; no. 3; pp. 339 - 344
• Main Authors: Blakesley, V A, Stannard, B S, Kalebic, T, Helman, L J, LeRoith, D
• Format: Journal Article
• Language: English
• Published: Colchester BioScientifica 01.03.1997; Portland Press
• Subjects: Animals; Apud cells. Peptide and protein hormones. Growth factors; Biological and medical sciences; Fundamental and applied biological sciences. Psychology; Gene Expression; Genes, Tumor Suppressor; Mice; Mutagenesis - physiology; Neoplasms - etiology; Oncogenes; Rats; Receptor, IGF Type 1 - physiology; REVIEW; Signal Transduction; Vertebrates: endocrinology; Cell proliferation; Insulin like growth factor; Mutagenesis; Peptidergic receptor; Review; Gene expression; Tumor promotion
• ISSN: 0022-0795; 1479-6805
• DOI: 10.1677/joe.0.1520339

Introduction The insulin-like growth factor-I (IGF-I) receptor is a transmembrane protein tyrosine kinase which mediates the biological effects of IGF-I (LeRoith et al. 1995, Nissley & Lopaczynski 1991) and most of the actions of insulinlike growth factor-II (IGF-II). Binding of IGF-I to the IGF-I receptor results in receptor autophosphorylation, phosphorylation of intracellular substrates and activation of specific signaling processes involved in growth regulation and differentiation (Lowe 1991). The role of the IGF-I receptor in normal mammalian development is exemplified by the work of Efstratiadis and co–workers on mice that carried a null mutation for the IGF-I receptor gene (Baker et al. 1993, Liu et al. 1993c). The growth in utero of these mice is severely inhibited and the mice die immediately after birth. Fibroblasts derived from these mice cannot grow in IGF-I-supplemented serum-free medium whereas mouse fibroblasts with functional IGF–I receptors are capable of growth (Sell et al. 1994), suggesting