title: Ets2 regulates colonic stem cells and sensitivity to tumorigenesis.
abstract: 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.
authors.affiliation: Tumor Development Program, Cancer Research Center, Sanford-Burnham Medical Research Institute, La Jolla, California 92037, USA.
authors.forename: Jorge
authors.initials: J
authors.lastname: Múnera
authors.forename: Grace
authors.initials: G
authors.lastname: Ceceña
authors.forename: Paul
authors.initials: P
authors.lastname: Jedlicka
authors.forename: Miriam
authors.initials: M
authors.lastname: Wankell
authors.forename: Robert G
authors.initials: RG
authors.lastname: Oshima
mesh_terms: D000236:Adenoma / Q000235:genetics* / Q000473:pathology; D053687:Adult Stem Cells / Q000378:metabolism / Q000473:pathology*; D000818:Animals; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000235:genetics* / Q000378:metabolism; D002478:Cells, Cultured; D003106:Colon / Q000166:cytology* / Q000378:metabolism / Q000473:pathology; D003110:Colonic Neoplasms / Q000235:genetics* / Q000473:pathology; D015536:Down-Regulation / Q000235:genetics / Q000502:physiology; D005260:Female; D020022:Genetic Predisposition to Disease; D007413:Intestinal Mucosa / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009928:Organ Specificity / Q000235:genetics; D050787:Proto-Oncogene Protein c-ets-2 / Q000235:genetics / Q000378:metabolism / Q000502:physiology*
chemical_list: C494070:Ets2 protein, mouse; D050787:Proto-Oncogene Protein c-ets-2