Loss of Apc in vivo immediately perturbs Wnt signaling, differentiation, and migration.
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.
Sansom
Owen J
OJ
School of Biosciences, University of Cardiff, Cardiff CF10 3US, Wales.
Reed
Karen R
KR
Hayes
Anthony J
AJ
Ireland
Heather
H
Brinkmann
Hannah
H
Newton
Ian P
IP
Batlle
Eduard
E
Simon-Assmann
Patricia
P
Clevers
Hans
H
Nathke
Inke S
IS
Clarke
Alan R
AR
Winton
Douglas J
DJ
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
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