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

Muncan, V. and Sansom, O.J. and Tertoolen, L. and Phesse, T.J. and Begthel, H. and Sancho, E. and Cole, A.M. and Gregorieff, A. and Alboran, I.M. de and Clevers, J.C. and Clarke, A.R. (2006) Rapid loss of intestinal crypts upon conditional deletion of the Wnt/Tcf-4 target gene c-Myc. Molecular and cellular biology, 26(22), 8418-8426. ISSN 02707306. doi: 10.1128/MCB.00821-06. PMC_URL: http://www.pubmedcentral.nih.gov/picrender.fcgi?tool=pmcentrez&artid=1636776&blobtype=pdf.

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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
Additional Information:doi: 10.1128/MCB.00821-06. PMC_URL: http://www.pubmedcentral.nih.gov/picrender.fcgi?tool=pmcentrez&artid=1636776&blobtype=pdf
Institutes:Hubrecht Instituut
ID Code:3590
Deposited On:13 Feb 2009 17:14
Last Modified:10 Dec 2009 13:14

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