title: Loss of Apc in vivo immediately perturbs Wnt signaling, differentiation, and migration.
abstract: 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.
authors.affiliation: School of Biosciences, University of Cardiff, Cardiff CF10 3US, Wales.
authors.forename: Owen J
authors.initials: OJ
authors.lastname: Sansom
authors.forename: Karen R
authors.initials: KR
authors.lastname: Reed
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Hayes
authors.forename: Heather
authors.initials: H
authors.lastname: Ireland
authors.forename: Hannah
authors.initials: H
authors.lastname: Brinkmann
authors.forename: Ian P
authors.initials: IP
authors.lastname: Newton
authors.forename: Eduard
authors.initials: E
authors.lastname: Batlle
authors.forename: Patricia
authors.initials: P
authors.lastname: Simon-Assmann
authors.forename: Hans
authors.initials: H
authors.lastname: Clevers
authors.forename: Inke S
authors.initials: IS
authors.lastname: Nathke
authors.forename: Alan R
authors.initials: AR
authors.lastname: Clarke
authors.forename: Douglas J
authors.initials: DJ
authors.lastname: Winton
mesh_terms: D025601:Adenomatous Polyposis Coli Protein / Q000172:deficiency*; D000818:Animals; D002454:Cell Differentiation; D002465:Cell Movement; D003598:Cytoskeletal Proteins / Q000378:metabolism; D007150:Immunohistochemistry; D007413:Intestinal Mucosa / Q000166:cytology; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D010641:Phenotype; D011518:Proto-Oncogene Proteins / Q000502:physiology*; D012333:RNA, Messenger / Q000032:analysis / Q000302:isolation & purification; D015398:Signal Transduction; D015534:Trans-Activators / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000172:deficiency; D051153:Wnt Proteins; D051176:beta Catenin
chemical_list: D025601:Adenomatous Polyposis Coli Protein; C495267:CTNNB1 protein, mouse; D003598:Cytoskeletal Proteins; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D015534:Trans-Activators; D025521:Tumor Suppressor Proteins; D051153:Wnt Proteins; D051176:beta Catenin