Crypt stem cells as the cells-of-origin of intestinal cancer.
Nature. 2009 Jan 29;457(7229):608-11. doi: 10.1038/nature07602. Epub 2008 Dec 17.
Barker N, Ridgway RA, van Es JH, van de Wetering M, Begthel H, van den Born M, Danenberg E, Clarke AR, Sansom OJ, Clevers H.
Intestinal cancer is initiated by Wnt-pathway-activating mutations in genes such as adenomatous polyposis coli (APC). As in most cancers, the cell of origin has remained elusive. In a cheap jerseys previously established Lgr5 (leucine-rich-repeat containing G-protein-coupled receptor 5) knockin mouse model, a tamoxifen-inducible Cre recombinase is expressed in long-lived cheap mlb jerseys intestinal stem cells. Here 9200 we show that deletion of Apc in these cheap jerseys stem cells leads to their transformation within days. Transformed stem cells remain located at crypt bottoms, while fuelling a growing microadenoma. These microadenomas show unimpeded growth and develop into macroscopic adenomas within 3-5 weeks. The distribution of Lgr5(+) cells within stem-cell-derived adenomas indicates that a stem cell/progenitor cell hierarchy is maintained in Friday early neoplastic lesions. forcing When Apc is deleted in short-lived transit-amplifying cells using a different stem cre mouse, cheap jerseys China the growth of the induced microadenomas cheap nba jerseys rapidly stalls. Even after 30 weeks, large adenomas are very rare in these mice. We conclude that stem-cell-specific loss of Apc results in progressively growing neoplasia.