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

Muncan, V. et al. (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. (doi: 10.1125/MCB.00821-06)

Abstract

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.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Sansom, Professor Owen
• Authors: Muncan, V., Sansom, O., Tertoolen, L., Phesse, T., Begthel, H., Sancho, E., Cole, A., Gregorieff, A., de Alboran, I., Clevers, H., and Clarke, A.
• College/School: College of Medical Veterinary and Life Sciences > School of Cancer Sciences
• Journal Name: Molecular and Cellular Biology
• ISSN: 0270-7306