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Genes & Dev. 19 (3): 311-315

Copyright © 2005 by Cold Spring Harbor Laboratory Press.

RESEARCH COMMUNICATION

Foxl1 is a mesenchymal Modifier of Min in carcinogenesis of stomach and colon

Nathalie Perreault1,4, Sara D. Sackett1,4, Jonathan P. Katz1,2, Emma E. Furth3, and Klaus H. Kaestner1,5

Departments of 1 Genetics and 2 Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, 19104-6145, USA; 3 Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104-4283, USA

Abstract: Constitutive activation of the Wnt/APC/{beta}-catenin pathway is a frequent initiating event in gastrointestinal carcinogenesis. Mutations in the Adenomatous Polyposis Coli (APC) gene up-regulate Wnt signaling by stabilizing {beta}-catenin and causing activation of targets important in proliferation control. Here we show that loss of the mesenchymal transcription factor Foxl1 leads to a marked increase in tumor multiplicity in the colon of ApcMin mice. ApcMin/+;Foxl1-/- mice also develop gastric tumors not observed in ApcMin mice. These effects are caused by earlier tumor initiation due to accelerated loss of heterozygosity (LOH) at the Apc locus. Foxl1 is the first mesenchymal Modifier of Min and plays a key role in gastrointestinal tumorigenesis.

Key Words: APC • FAP • FOXL1 • LOH • {beta}-catenin

Received for publication September 10, 2004. Accepted for publication December 1, 2004.

Article published online ahead of print. Article and publication date are at http://www.genesdev.org/cgi/doi/10.1101/gad.1260605.

4 These authors have contributed equally to this work.

5 Corresponding author.
E-MAIL kaestner{at}mail.med.upenn.edu; FAX (215) 573-5892.

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