ACTIVATION OF WNT?}?Ò-CATENIN SIGNALING PATHWAY IN THE LIVER OF TRANSGENIC MICE OVEREXPRESSING GROWTH HORMONE

MIQUET JG; MARTÍNEZ CS; GONZALEZ L; DÍAZ ME; ZOTTA E; BARTKE A; TURYN D; SOTELO AI

Berlin

Congreso; International Liver Congress TM 2011; 2011

BACKGROUND AND AIMS: Transgenic mice overexpressing growth hormone (GH) exhibit hepatomegaly due to hypertrophy and hyperplasia. Throughout lifespan, transgenic mice present high levels of hepatocellular replication and at advanced ages develop liver tumors, mainly hepatocellular carcinoma (HCC). Wnt/b-catenin signaling regulates cell proliferation, apoptosis and differentiation, and is believed to play a role in carcinogenesis. A high percentage of human HCC show high levels of b-catenin, usually located at the cytoplasm or nucleus rather than at the plasma membrane. Control of b-catenin stability is regulated by GSK-3b, which phosphorylates b-catenin, promoting its degradation. The objective of this work was to evaluate if Wnt/b-catenin signaling is dysregulated in the liver of GH-transgenic mice to assess its possible association with the liver pathology observed in these animals. METHODS: Young adult transgenic mice overexpressing GH, which present preneoplastic liver pathology, were studied; non-transgenic siblings were used as controls. Liver samples were subjected to qRT-PCR, Western-blotting and immunohistochemistry to evaluate gene expression, protein content and cellular localization of the mediators under study. RESULTS: b-catenin protein content was 2-fold increased in the liver of GH-overexpressing mice, although its mRNA levels were lower compared to normal siblings (P