Loss of Apc in vivo immediately perturbs Wnt signaling, differentiation, and migration.
Sansom OJ,
Reed KR,
Hayes AJ,
Ireland H,
Brinkmann H,
Newton IP,
Batlle E,
Simon-Assmann P,
Clevers H,
Nathke IS,
Clarke AR,
Winton DJ.
School of Biosciences, University of Cardiff, Cardiff CF10 3US, Wales.
Although Apc is well characterized as a tumor-suppressor gene in the intestine, the precise mechanism of this suppression remains to be defined. Using a novel inducible Ahcre transgenic line in conjunction with a loxP-flanked Apc allele we, show that loss of Apc acutely activates Wnt signaling through the nuclear accumulation of beta-catenin. Coincidentally, it perturbs differentiation, migration, proliferation, and apoptosis, such that Apc-deficient cells maintain a "crypt progenitor-like" phenotype. Critically, for the first time we confirm a series of Wnt target molecules in an in vivo setting and also identify a series of new candidate targets within the same setting.
PMID: 15198980 [PubMed - indexed for MEDLINE]
PMCID: PMC423189