Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2009 Jan 29;457(7229):608-11.
doi: 10.1038/nature07602. Epub 2008 Dec 17.

Crypt stem cells as the cells-of-origin of intestinal cancer

Nick Barker  1 , Rachel A Ridgway, Johan H van Es, Marc van de Wetering, Harry Begthel, Maaike van den Born, Esther Danenberg, Alan R Clarke, Owen J Sansom, Hans Clevers
Affiliations

Crypt stem cells as the cells-of-origin of intestinal cancer

Nick Barker et al. Nature. .

Abstract

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 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 intestinal stem cells. Here we show that deletion of Apc in these 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 3-5weeks. The distribution of Lgr5(+) cells within stem-cell-derived adenomas indicates that a stem cell/progenitor cell hierarchy is maintained in early neoplastic lesions. When Apc is deleted in short-lived transit-amplifying cells using a different cre mouse, the growth of the induced microadenomas rapidly stalls. Even after 30weeks, large adenomas are very rare in these mice. We conclude that stem-cell-specific loss of Apc results in progressively growing neoplasia.

PubMed Disclaimer

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Bull Cancer. 1975 Oct-Dec;62(4):419-30 - PubMed
    1. Proc Natl Acad Sci U S A. 2003 Apr 1;100(7):3983-8 - PubMed
    1. Dev Dyn. 2005 Aug;233(4):1332-6 - PubMed
    1. Am J Anat. 1974 Dec;141(4):461-79 - PubMed
    1. Genes Dev. 2004 Jun 15;18(12):1385-90 - PubMed

Publication types

MeSH terms