Journal
SCIENCE
Volume 307, Issue 5717, Pages 1976-1978Publisher
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.1108080
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Funding
- NCI NIH HHS [K08CA106610, R01CA65145] Funding Source: Medline
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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 lgf2 LOI by crossing female H19(+/-) mice with mate 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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