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

Takashi Sakatani, Atsushi Kaneda, Christine A. Iacobuzio-Donahue, Mark G. Carter, Sten De Boom Witzel, Hideyuki Okano, Minora S.H. Ko, Rolf Ohlsson, Dan L. Longo, Andrew P. Feinberg

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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.

Original languageEnglish
Pages (from-to)1976-1978
Number of pages3
JournalScience
Volume307
Issue number5717
DOIs
Publication statusPublished - 2005 Mar 25

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Sakatani, T., Kaneda, A., Iacobuzio-Donahue, C. A., Carter, M. G., De Boom Witzel, S., Okano, H., Ko, M. S. H., Ohlsson, R., Longo, D. L., & Feinberg, A. P. (2005). Loss of imprinting of Igf2 alters intestinal maturation and tumorigenesis in mice. Science, 307(5717), 1976-1978. https://doi.org/10.1126/science.1108080