The H19 locus acts in vivo as a tumor suppressor

Proc Natl Acad Sci U S A. 2008 Aug 26;105(34):12417-22. doi: 10.1073/pnas.0801540105. Epub 2008 Aug 21.

Abstract

The H19 locus belongs to a cluster of imprinted genes that is linked to the human Beckwith-Wiedemann syndrome. The expression of H19 and its closely associated IGF2 gene is frequently deregulated in some human tumors, such as Wilms' tumors. In these cases, biallelic IGF2 expression and lack of expression of H19 are associated with hypermethylation of the imprinting center of this locus. These observations and others have suggested a potential tumor suppressor effect of the H19 locus. Some studies have also suggested that H19 is an oncogene, based on tissue culture systems. We show, using in vivo murine models of tumorigenesis, that the H19 locus controls the size of experimental teratocarcinomas, the number of polyps in the Apc murine model of colorectal cancer and the timing of appearance of SV40-induced hepatocarcinomas. The H19 locus thus clearly displays a tumor suppressor effect in mice.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carcinoma, Hepatocellular / pathology
  • Colorectal Neoplasms / pathology
  • Disease Models, Animal
  • Genes, Tumor Suppressor / physiology*
  • Insulin-Like Growth Factor II
  • Mice
  • Mice, Mutant Strains
  • Multigene Family
  • RNA, Long Noncoding
  • RNA, Untranslated / classification
  • RNA, Untranslated / physiology*
  • Teratoma / pathology

Substances

  • H19 long non-coding RNA
  • IGF2 protein, mouse
  • RNA, Long Noncoding
  • RNA, Untranslated
  • Insulin-Like Growth Factor II