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Gastroenterology. 2003 Jan;124(1):202-16.

Beta-catenin antisense studies in embryonic liver cultures: role in proliferation, apoptosis, and lineage specification.

Author information

1
Department of Cellular and Molecular Pathology, S421-BST, University of Pittsburgh School of Medicine, 200 Lothrop Street, Pittsburgh, PA 15261, USA. smonga@pitt.edu

Abstract

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. Beta-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.

PMID:
12512043
DOI:
10.1053/gast.2003.50000
[Indexed for MEDLINE]

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