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Mol Cell Biol. 2006 Nov;26(22):8418-26. Epub 2006 Sep 5.

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

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1
Hubrecht Laboratory, Nederlands Institute for Developmental Biology, Uppsalalaan 8, 3584 CT Utrecht, The Netherlands.

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.

PMID:
16954380
PMCID:
PMC1636776
DOI:
10.1128/MCB.00821-06
[Indexed for MEDLINE]
Free PMC Article
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