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Cancer Stem Cells
Version of Record online: 21 MAR 2011
Copyright © 2011 AlphaMed Press
Volume 29, Issue 3, pages 430–439, March 2011
How to Cite
Múnera, J., Ceceña, G., Jedlicka, P., Wankell, M. and Oshima, R. G. (2011), Ets2 Regulates Colonic Stem Cells and Sensitivity to Tumorigenesis. STEM CELLS, 29: 430–439. doi: 10.1002/stem.599
Disclosure of potential conflicts of interest is found at the end of this article.
Author contributions: J.M.: conception and design, collection and/or assembly of data, data analysis and interpretation, manuscript composition; G.C.: collection and/or assembly of data; P.J.: data analysis; M.W.: collection and/or assembly of data; R.G.O.: conception and design, data analysis and interpretation, manuscript composition.
First published online in STEM CELLSEXPRESS January 14, 2011.
- Issue online: 21 MAR 2011
- Version of Record online: 21 MAR 2011
- Accepted manuscript online: 14 JAN 2011 12:27PM EST
- Manuscript Accepted: 20 DEC 2010
- Manuscript Received: 5 AUG 2010
- Stem cells;
- Crypt fission;
Ets2 has both tumor repressive and supportive functions for different types of cancer. We have investigated the role of Ets2 within intestinal epithelial cells in postnatal mouse colon development and tumorigenesis. Conditional inactivation of Ets2 within intestinal epithelial cells results in over representation of Ets2-deficient colon crypts within young and adult animals. This preferential representation is associated with an increased number of proliferative cells within the stem cell region and an increased rate of crypt fission in young mice that result in larger patches of Ets2-deficient crypts. These effects are consistent with a selective advantage of Ets2-deficient intestinal stem cells in colonizing colonic crypts and driving crypt fission. Ets2-deficient colon crypts have an increased mucosal thickness, an increased number of goblet cells, and an increased density. Mice with Ets2-deficient intestinal cells develop more colon tumors in response to treatment with azoxymethane and dextran sulfate sodium. The selective population of colon crypts, the altered differentiation state and increased sensitivity to carcinogen-induced tumors all indicate that Ets2 deficiency alters colon stem cell number or behavior. Ets2-dependent, epithelial cell-autonomous repression of intestinal tumors may contribute to protection from colon cancer of persons with increased dosage of chromosome 21. STEM CELLS 2011;430–439