β-catenin antisense studies in embryonic liver cultures: role in proliferation, apoptosis, and lineage specification
SPS Monga, HK Monga, X Tan, K Mulé, P Pediaditakis… - Gastroenterology, 2003 - Elsevier
Gastroenterology, 2003•Elsevier
Background & Aims: Wnt/β-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 β-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 β-catenin antisense phosphorodiamidate morpholino oligomer (PMO) were
used to elucidate the role of β-catenin in liver development. Livers from embryos at 10 days …
hepatoblastomas, hepatocellular cancers, and liver regeneration. The aim of this study was
to investigate the role of β-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 β-catenin antisense phosphorodiamidate morpholino oligomer (PMO) were
used to elucidate the role of β-catenin in liver development. Livers from embryos at 10 days …
Background & Aims
Wnt/β-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 β-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 β-catenin antisense phosphorodiamidate morpholino oligomer (PMO) were used to elucidate the role of β-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
β-Catenin shows stage-specific localization and distinct distribution compared with known markers in developing liver. A substantial decrease in β-catenin protein was evident in the organs cultured in the presence of antisense. β-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. β-Catenin inhibition also promoted c-kit immunoreactivity of the hepatocytes.
Conclusions
We conclude that the PMO antisense to β-catenin effectively inhibits synthesis of its protein. β-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.
Elsevier