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Loss of imprinting of Igf2 alters intestinal maturation and tumorigenesis in mice.

Authors
  • Sakatani, Takashi
  • Kaneda, Atsushi
  • Iacobuzio-Donahue, Christine A
  • Carter, Mark G
  • de Boom Witzel, Sten
  • Okano, Hideyuki
  • Ko, Minoru S H
  • Ohlsson, Rolf
  • Longo, Dan L
  • Feinberg, Andrew P
Type
Published Article
Journal
Science
Publisher
American Association for the Advancement of Science (AAAS)
Publication Date
Mar 25, 2005
Volume
307
Issue
5717
Pages
1976–1978
Identifiers
PMID: 15731405
Source
Medline
License
Unknown

Abstract

Loss of imprinting (LOI) of the insulin-like growth factor II gene (IGF2) is an epigenetic alteration that results in a modest increase in IGF2 expression, and it is present in the normal colonic mucosa of about 30% of patients with colorectal cancer. To investigate its role in intestinal tumorigenesis, we created a mouse model of Igf2 LOI by crossing female H19+/- mice with male Apc+/Min mice. Mice with LOI developed twice as many intestinal tumors as did control littermates. Notably, these mice also showed a shift toward a less differentiated normal intestinal epithelium, reflected by an increase in crypt length and increased staining with progenitor cell markers. A similar shift in differentiation was seen in the normal colonic mucosa of humans with LOI. Thus, altered maturation of nonneoplastic tissue may be one mechanism by which epigenetic changes affect cancer risk.

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