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Hepatomegaly in Transgenic Mice Expressing an Oncogenic Form of ß-Catenin¹

Institut Cochin de Génétique Moléculaire INSERM U129, 75014 Paris [A. C., C. O., S. S-K., E. S., B. R., A. K., C. P.], and Laboratoire d’Anatomopathologie du Professeur Bedossa, Hôpital Bicêtre, 94275 Le Kremlin-Bicêtre [M. F.], France

Inappropriate activation of the Wnt/ß-catenin signaling, resulting mainly from activating mutations of the ß-catenin gene, has been implicated recently in the development of hepatocellular carcinoma (HCC). We have generated transgenic mice expressing an oncogenic form of ß-catenin in their hepatocytes to analyze the effect of deregulated ß-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 ß-catenin signaling pathway, neither of them was overexpressed in the hyperplastic livers of ß-catenin transgenic mice. Thus, the key target genes of the ß-catenin signaling pathway in the liver remain to be identified.

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