Microsatellite Analysis of the Insulin-Like Growth Factor II Receptor in Colorectal Carcinomas

Abstract

The insulin-like growth factor II (IGFII) growth control pathway is comprised of three major components: IGFII ligand, insulin-like growth factor I receptor (IGFIR), and insulin-like growth factor II receptor (IGFIIR). IGFIR and IGFIIR work together to maintain constant circulating levels of IGFII. IGFII is a potent mitogen, produced by epithelial cells, which stimulates cell growth and prevents apoptosis by binding to IGFIR (1,2). IGFIR is a member of the receptor tyrosine kinase family (3) Upon binding IGFII, IGFIR autophosphorylates tyrosine residues, thereby initiating signaling Fig. 1 ) (3). Both mitogenic and anti-apoptotic signaling pathways are initiated by the binding of IGFII to IGFIR (3). Fig. 1. The Insulin-Like Growth Factor II pathway. IGFII ligand binds IGFIR thereby initiating a signaling cascade which is both mitogenic and anti-apoptotic. IGFIIR counterbalances these mitogenic and anti-apoptotic effects by binding, internalizing, and degrading IGFII thus making IGFII unavailable to activate IGFIR. IGFIR and IGFIIR work together to maintain constant circulating leveles of IGFII.