PTEN-deficient intestinal stem cells initiate intestinal polyposis
| Autor: | Qiang Tian, Leroy Hood, Terrence A. Barrett, Leanne M. Wiedemann, Tong Yin, Mark Hembree, Hong Wu, Teri Johnson, Raminarao Dirisina, Kimberly S. Porter-Westpfahl, Linheng Li, Xi C. He, Toshiro Sato, W. Andy Tao, Justin C. Grindley |
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| Rok vydání: | 2007 |
| Předmět: |
inorganic chemicals
Beta-catenin Tumor suppressor gene Intestinal polyp Cell Count digestive system Article Mice Genetics Animals PTEN Tensin Intestinal Mucosa Phosphorylation Protein kinase B beta Catenin Cell Nucleus biology Stem Cells Cell Cycle PTEN Phosphohydrolase Wnt signaling pathway Intestinal Polyps biology.protein Cancer research Stem cell Proto-Oncogene Proteins c-akt |
| Zdroj: | Nature Genetics. 39:189-198 |
| ISSN: | 1546-1718 1061-4036 |
| DOI: | 10.1038/ng1928 |
| Popis: | Intestinal polyposis, a precancerous neoplasia, results primarily from an abnormal increase in the number of crypts, which contain intestinal stem cells (ISCs). In mice, widespread deletion of the tumor suppressor Phosphatase and tensin homolog (PTEN) generates hamartomatous intestinal polyps with epithelial and stromal involvement. Using this model, we have established the relationship between stem cells and polyp and tumor formation. PTEN helps govern the proliferation rate and number of ISCs and loss of PTEN results in an excess of ISCs. In PTEN-deficient mice, excess ISCs initiate de novo crypt formation and crypt fission, recapitulating crypt production in fetal and neonatal intestine. The PTEN-Akt pathway probably governs stem cell activation by helping control nuclear localization of the Wnt pathway effector beta-catenin. Akt phosphorylates beta-catenin at Ser552, resulting in a nuclear-localized form in ISCs. Our observations show that intestinal polyposis is initiated by PTEN-deficient ISCs that undergo excessive proliferation driven by Akt activation and nuclear localization of beta-catenin. |
| Databáze: | OpenAIRE |
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