Hepatomegaly in transgenic mice expressing an oncogenic form of beta-catenin

Inappropriate activation of the Wnt/beta -catenin signaling, resulting main ly from activating mutations of the beta -catenin gene, has been implicated recently in the development of hepatocellular carcinoma (HCC). We have gen erated transgenic mice expressing an oncogenic form of beta -catenin in the ir 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 proli feration without any compensatory apoptosis, Although the genes encoding c- myc and cyclin D1 are potential targets of the beta -catenin signaling path way, neither of them was overexpressed in the hyperplastic livers of beta - catenin transgenic mice. Thus, the key target genes of the beta -catenin si gnaling pathway in the liver remain to be identified.