Deregulation of both imprinted and expressed alleles of the insulin-like growth factor 2 gene during beta-cell tumorigenesis

Nat Genet. 1995 Jun;10(2):196-201. doi: 10.1038/ng0695-196.

Abstract

In a mouse model of multistage carcinogenesis elicited by the SV40 large T-antigen (Tag) oncogene in pancreatic beta cells, the gene for insulin-like growth factor IGF2 is focally up-regulated and functionally implicated in tumour development. The IGF2 gene is differentially regulated in normal tissues: the paternal allele is transiently expressed during embryogenesis, whereas the maternal allele is genomically imprinted and inactive. Crossbred mice carrying the Tag oncogene and a disruption of either the paternal or maternal allele of IGF2 reveal that both alleles are co-activated early during tumour development, and that each contributes to malignant hyperproliferation and consequent tumour volume.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Alleles
  • Animals
  • Base Sequence
  • Cell Transformation, Neoplastic / genetics*
  • Gene Expression Regulation, Neoplastic
  • Genomic Imprinting*
  • Genotype
  • Insulin-Like Growth Factor II / biosynthesis
  • Insulin-Like Growth Factor II / genetics*
  • Islets of Langerhans / cytology
  • Islets of Langerhans / metabolism
  • Islets of Langerhans / pathology
  • Mice
  • Mice, Inbred Strains
  • Mice, Knockout
  • Mice, Transgenic
  • Molecular Sequence Data
  • Muscle Proteins / biosynthesis
  • Muscle Proteins / genetics
  • Pancreatic Neoplasms / genetics
  • Pancreatic Neoplasms / pathology*
  • Phenotype
  • RNA, Long Noncoding
  • RNA, Messenger / biosynthesis
  • RNA, Untranslated*
  • Up-Regulation

Substances

  • H19 long non-coding RNA
  • Muscle Proteins
  • RNA, Long Noncoding
  • RNA, Messenger
  • RNA, Untranslated
  • Insulin-Like Growth Factor II