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RESEARCH COMMUNICATION
1 School of Biosciences, University of Cardiff, Cardiff CF10 3US, Wales; 2 Cancer Research UK Department of Oncology, Cambridge CB2 2XY, UK; 3 School of Life Sciences, University of Dundee, Dundee DD1 5EH, Scotland; 4 Hubrecht Laboratory, 3584 CT Utrecht, The Netherlands; 5 INSERM U381, Strasbourg, France.
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
-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.
[Keywords: Apc; Wnt signaling; intestine; conditional; apoptosis]
Received October 3, 2003; revised version accepted April 19, 2004.
Article and publication are at http://www.genesdev.org/cgi/doi/10.1101/gad.287404.
6 Corresponding author. E-MAIL clarkear{at}cf.ac.uk; FAX 44-0-2920-874116.
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