The role of insulin-like growth factor 2 and its receptors in human tumors.

Insulin-like growth factor 2 (IGF-2) is important for normal development and growth of an organism. In humans it is encoded by 11p15.5 paternally expressed imprinted gene. It binds at least two different types of receptors: IGF type 1 (IGF-1R) and IGF-2/mannose 6-phosphate receptors (IGF-2R/M6P). Ligand binding to IGF-1R provokes mitogenic and anti-apoptotic effects. IGF-2R/M6P has tumor suppressor function; it mediates IGF-2 degradation. When the IGF-2 gene/protein is overexpressed, mostly as a consequence of loss of heterozygosity resulting in paternal allele duplication (LOH) or by loss of imprinting (LOI), it is involved in the development and progression of many tumors and overgrowth syndromes by autocrine or paracrine mechanisms.