IGF2: epigenetic regulation and role in development and disease

Cytokine Growth Factor Rev. 2008 Apr;19(2):111-20. doi: 10.1016/j.cytogfr.2008.01.005. Epub 2008 Mar 4.


Insulin-like growth factor II (IGF2) is perhaps the most intricately regulated of all growth factors characterized to date. Its gene is imprinted--only one allele is active, depending on parental origin--and this pattern of expression is maintained epigenetically in almost all tissues. IGF2 activity is further controlled through differential expression of receptors and IGF-binding proteins (IGFBPs) that determine protein availability. This complex and multifaceted regulation emphasizes the importance of accurate IGF2 expression and activity. This review will examine the regulation of the IGF2 gene and what it has revealed about the phenomenon of imprinting, which is frequently disrupted in cancer. IGF2 protein function will be discussed, along with diseases that involve IGF2 overexpression. Roles for IGF2 in sonic hedgehog (Shh) signaling and angiogenesis will also be explored.

Publication types

  • Review

MeSH terms

  • Alleles
  • Animals
  • Binding Sites
  • Cell Differentiation
  • Epigenesis, Genetic*
  • Gene Expression Regulation, Developmental*
  • Genomic Imprinting
  • Hedgehog Proteins / metabolism
  • Humans
  • Insulin-Like Growth Factor II / genetics*
  • Insulin-Like Growth Factor II / metabolism
  • Insulin-Like Growth Factor II / physiology*
  • Models, Biological
  • Neovascularization, Pathologic
  • Neovascularization, Physiologic
  • Signal Transduction
  • Vascular Endothelial Growth Factor A / metabolism


  • Hedgehog Proteins
  • Vascular Endothelial Growth Factor A
  • Insulin-Like Growth Factor II