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

TY - JOUR

T1 - Rapid loss of intestinal crypts upon conditional deletion of the Wnt/Tcf-4 target gene c-Myc.

AU - Muncan, V.

AU - Sansom, O.J.

AU - Tertoolen, L.

AU - Phesse, T.J.

AU - Begthel, H.

AU - Sancho, E.

AU - Cole, A.M.

AU - Gregorieff, A.

AU - Alboran, I.M. de

AU - Clevers, J.C.

AU - Clarke, A.R.

N1 - doi: 10.1128/MCB.00821-06. PMC_URL: http://www.pubmedcentral.nih.gov/picrender.fcgi?tool=pmcentrez&artid=1636776&blobtype=pdf

PY - 2006

Y1 - 2006

N2 - 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.

AB - 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.

M3 - Article

SN - 0270-7306

VL - 26

SP - 8418

EP - 8426

JO - Molecular and Cellular Biology

JF - Molecular and Cellular Biology

ER -