Hepatomegaly in transgenic mice expressing an oncogenic form of beta-catenin.
Inappropriate activation of the Wnt/beta-catenin signaling, resulting mainly from activating mutations of the beta-catenin gene, has been implicated recently in the development of hepatocellular carcinoma (HCC). We have generated transgenic mice expressing an oncogenic form of beta-catenin in their hepatocytes to analyze the effect of deregulated beta-catenin signaling on liver homeostasis. These mice rapidly developed hepatomegaly soon after birth, with livers three to four times heavier than those of nontransgenic littermates. The liver cell hyperplasia resulted from increased cell proliferation without any compensatory apoptosis. Although the genes encoding c-myc and cyclin D1 are potential targets of the beta-catenin signaling pathway, neither of them was overexpressed in the hyperplastic livers of beta-catenin transgenic mice. Thus, the key target genes of the beta-catenin signaling pathway in the liver remain to be identified.
Cadoret
A
A
Institut Cochin de Génétique Moléculaire INSERM U129, 75014 Paris, France.
Ovejero
C
C
Saadi-Kheddouci
S
S
Souil
E
E
Fabre
M
M
Romagnolo
B
B
Kahn
A
A
Perret
C
C
D000818:Animals; D017209:Apoptosis / Q000502:physiology; D002455:Cell Division / Q000502:physiology; D019938:Cyclin D1 / Q000096:biosynthesis / Q000235:genetics; D003598:Cytoskeletal Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D005786:Gene Expression Regulation; D019940:Genes, bcl-1; D016259:Genes, myc; D006529:Hepatomegaly / Q000235:genetics* / Q000378:metabolism; D008099:Liver / Q000378:metabolism / Q000473:pathology* / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D008822:Mice, Transgenic; D009154:Mutation; D016271:Proto-Oncogene Proteins c-myc / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015534:Trans-Activators; D051176:beta Catenin
C495267:CTNNB1 protein, mouse; D003598:Cytoskeletal Proteins; D016271:Proto-Oncogene Proteins c-myc; D015534:Trans-Activators; D051176:beta Catenin; D019938:Cyclin D1