Rapid loss of intestinal crypts upon conditional deletion of the Wnt/Tcf-4 target gene c-Myc

Muncan, Vanesa, Sansom, Owen J. ORCID: https://orcid.org/0000-0001-9540-3010, Tertoolen, Leon, Phesse, Toby ORCID: https://orcid.org/0000-0001-9568-4916, Begthel, Harry, Sancho, Elena, Cole, Alicia M., Gregorieff, Alex, de Alboran, Ignacio Moreno, Clevers, Hans and Clarke, Alan Richard ORCID: https://orcid.org/0000-0002-4281-426X 2006. Rapid loss of intestinal crypts upon conditional deletion of the Wnt/Tcf-4 target gene c-Myc. Molecular and Cellular Biology 26 (22) , pp. 8418-8426. 10.1128/MCB.00821-06

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Abstract

Inhibition of the mutationally activated Wnt cascade in colorectal cancer cell lines induces a rapid G1 arrest and subsequent differentiation. This arrest can be overcome by maintaining expression of a single Tcf4 target gene, the proto-oncogene c-Myc. Since colorectal cancer cells share many molecular characteristics with proliferative crypt progenitors, we have assessed the physiological role of c-Myc in adult crypts by conditional gene deletion. c-Myc-deficient crypts are lost within weeks and replaced by c-Myc-proficient crypts through a fission process of crypts that have escaped gene deletion. Although c-Myc−/− crypt cells remain in the cell cycle, they are on average much smaller than wild-type cells, cycle slower, and divide at a smaller cell size. c-Myc appears essential for crypt progenitor cells to provide the necessary biosynthetic capacity to successfully progress through the cell cycle.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Biosciences European Cancer Stem Cell Research Institute (ECSCRI)
Subjects:	Q Science > Q Science (General)
Publisher:	American Society for Microbiology
ISSN:	0270-7306
Last Modified:	29 Jun 2023 17:06
URI:	https://orca.cardiff.ac.uk/id/eprint/61347

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