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Introduction
Insulin-like growth factor-II (IGF-II) is a regulatory peptide which is critical for normal organismal growth and differentiation, and which is implicated in tumor progression and metastasis by a variety of mechanisms, in many otherwise unrelated tumors. IGF-II signaling pathways involve two specific receptors. A family of six unique binding proteins for IGF-II exist, as well as binding protein proteases which, in turn, regulate IGF-II-binding protein levels. This report briefly describes the structural and functional characteristics of the IGF-II molecule and discusses the various mechanisms of IGF-II overactivity leading to tumor growth. Wilms' tumor, rhabdomyosarcoma, and neuroblastoma illustrate the involvement of IGF-II in tumor growth and metastasis. In tumors where IGF-II is thought to play a role in pathogenesis, the IGF-II signaling pathway may serve as a potential therapeutic target.
Components of the IGF-II signaling pathways
IGF-II overexpression The gene for human IGF-II is found on the short
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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
