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PMID: 15198980 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Loss of Apc in vivo immediately perturbs Wnt signaling, differentiation, and migration.

Genes & development ·Vol. 18 ·No. 12 ·2004-06-15 ·Pages 1385-90

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

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.

MeSH Terms
Adenomatous Polyposis Coli Protein/deficiency Animals Cell Differentiation Cell Movement Cytoskeletal Proteins/metabolism Immunohistochemistry Intestinal Mucosa/cytology Mice Mice, Knockout Mice, Transgenic Phenotype Proto-Oncogene Proteins/physiology RNA, Messenger/analysis,isolation & purification Signal Transduction Trans-Activators/metabolism Tumor Suppressor Proteins/deficiency Wnt Proteins beta Catenin
Chemicals
Adenomatous Polyposis Coli Protein CTNNB1 protein, mouse Cytoskeletal Proteins Proto-Oncogene Proteins RNA, Messenger Trans-Activators Tumor Suppressor Proteins Wnt Proteins beta Catenin
Authors & Affiliations
12 authors, click to expand affiliations / ORCID
Sansom Owen J
School of Biosciences, University of Cardiff, Cardiff CF10 3US, Wales.
Reed Karen R
Hayes Anthony J
Ireland Heather
Brinkmann Hannah
Newton Ian P
Batlle Eduard
Simon-Assmann Patricia
Clevers Hans
Nathke Inke S
Clarke Alan R
Winton Douglas J
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Article Info
Journal
Genes & development
Abbr.
Genes Dev
ISSN
0890-9369
DOI
10.1101/gad.287404
Published
2004-06-15
Pages
1385-90
Language
English
Region
United States
NLM ID
8711660
PMCID
PMC423189
Subset
IM
External Links
PubMed source DOI: 10.1101/gad.287404 PMC Full Text View journal details
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