Journal
GASTROENTEROLOGY
Volume 124, Issue 1, Pages 202-216Publisher
W B SAUNDERS CO-ELSEVIER INC
DOI: 10.1053/gast.2003.50000
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Funding
- NCI NIH HHS [R01 CA035373-21, CA 30241, CA 35373] Funding Source: Medline
- NATIONAL CANCER INSTITUTE [R01CA035373, R37CA030241, R01CA030241] Funding Source: NIH RePORTER
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Background & Aims: Wnt/beta-catenin pathway activation occurs during liver growth in hepatoblastomas, hepatocellular cancers, and liver regeneration. The aim of this study was to investigate the role of beta-catenin, a key component of the Wnt pathway, in liver development as well as its normal distribution in developing liver. Methods: Embryonic liver cultures and beta-catenin antisense phosphorodiamidate morpholino oligomer (PMO) were used to elucidate the role of beta-catenin in liver development. Livers from embryos at :10 days of gestational development were cultured in the presence of antisense or control PMO for 72 hours and analyzed. Results: beta-Catenin shows stage-specific localization and distinct distribution compared with known markers in developing liver. A substantial decrease in beta-catenin protein was evident in the organs cultured in the presence of antisense. beta-Catenin inhibition decreased cell proliferation and increased apoptosis in these organ cultures. Presence of antisense resulted in loss of CK19 immunoreactivity of the bipotential stem cells. R-Catenin inhibition also promoted c-kit immunoreactivity of the hepatocytes. Conclusions: We conclude that the PMO antisense to beta-catenin effectively inhibits synthesis of its protein. beta-Catenin modulates cell proliferation and apoptosis in developing liver. It may play a significant role in early biliary lineage commitment of the bipotential stem cells and also seems to be important in hepatocyte maturation.
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