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

First Author  Muncan V Year  2006
Journal  Mol Cell Biol Volume  26
Issue  22 Pages  8418-26
PubMed ID  16954380 Mgi Jnum  J:114673
Mgi Id  MGI:3689687 Doi  10.1128/MCB.00821-06
Citation  Muncan V, et al. (2006) Rapid Loss of Intestinal Crypts upon Conditional Deletion of the Wnt/Tcf-4 Target Gene c-Myc. Mol Cell Biol 26(22):8418-26
abstractText  Inhibition of the mutationally activated Wnt cascade in colorectal cancer cell lines induces a rapid G(1) 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.
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