Foxl1 is a mesenchymal Modifier of Min in carcinogenesis of stomach and colon.
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 Apc(Min) mice. Apc(Min/+);Foxl1-/- mice also develop gastric tumors not observed in Apc(Min) 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.
Perreault
Nathalie
N
Department of Genetics, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, 19104-6145, USA.
Sackett
Sara D
SD
Katz
Jonathan P
JP
Furth
Emma E
EE
Kaestner
Klaus H
KH
D000818:Animals; D003110:Colonic Neoplasms / Q000209:etiology / Q000235:genetics* / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism; D051858:Forkhead Transcription Factors; D017491:Genes, APC / Q000502:physiology; D019656:Loss of Heterozygosity; D051379:Mice; D013274:Stomach Neoplasms / Q000209:etiology / Q000235:genetics* / Q000378:metabolism; D014157:Transcription Factors / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism
D004268:DNA-Binding Proteins; D051858:Forkhead Transcription Factors; C099993:Foxl1 protein, mouse; D014157:Transcription Factors