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

V. Muncan, O.J. Sansom, L. Tertoolen, T.J. Phesse, H. Begthel, E. Sancho, A.M. Cole, A. Gregorieff, I.M. de Alboran, J.C. Clevers, A.R. Clarke

Research output: Contribution to journal/periodicalArticleScientificpeer-review

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.
Original languageEnglish
Pages (from-to)8418-8426
JournalMolecular and Cellular Biology
Volume26
Publication statusPublished - 2006

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