HBx inhibits the growth of CCL13-HBX-stable cells via the GSK-3beta/beta-catenin cascade.
OBJECTIVE
The hepatitis B virus X protein (HBx) plays critical roles in cell survival via modulation of signaling pathways. In our previous studies, we reported that HBx inhibited the growth of CCL13-HBx-stable cells (Chang-HBx cells) in vitro and tumor formation in vivo in CCL13-HBx-cell-injected nude mice; however, this inhibition mechanism is unclear.


METHODS
To investigate the role of HBx in Wnt-3/beta-catenin signaling pathways, we focused on the key molecules GSK-3beta and beta-catenin, and analyzed by Western blotting and immunofluorescence staining.


RESULTS
Results indicated that following HBx induction, GSK-3beta activity was up-regulated, the expression and accumulation of beta-catenin in the nucleus were decreased, and cell proliferation was suppressed. Inhibition of GSK-3beta activity by pharmacological inhibitors rescued the expression and accumulation of beta-catenin in the nucleus and facilitated cell proliferation and growth following HBx induction. The localization of beta-catenin, which is involved in cell proliferation, and mediated by GSK-3beta activation was also demonstrated.


CONCLUSIONS
Our findings suggest that HBx negatively regulated proliferation of CCL13-HBx-stable cells via the GSK-3beta/beta-catenin cascade.
Department of Life Science, Tunghai University, Taichung, Taiwan.
Chan-Yen
CY
Kuo
Cheng-Chung
CC
Wu
Shih-Lan
SL
Hsu
Guang-Yuh
GY
Hwang
D002467:Cell Nucleus / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D015536:Down-Regulation; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism*; D006515:Hepatitis B virus / Q000378:metabolism / Q000472:pathogenicity*; D022781:Hepatocytes / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D008099:Liver / Q000166:cytology; D018945:Monocyte Chemoattractant Proteins / Q000378:metabolism; D015534:Trans-Activators / Q000378:metabolism / Q000494:pharmacology*; D015854:Up-Regulation; D054334:Viral Regulatory and Accessory Proteins; D051176:beta Catenin / Q000378:metabolism*
C099677:CCL13 protein, human; D018945:Monocyte Chemoattractant Proteins; D015534:Trans-Activators; D054334:Viral Regulatory and Accessory Proteins; D051176:beta Catenin; C057628:hepatitis B virus X protein; D038362:Glycogen Synthase Kinase 3