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Hepatitis B virus X protein promotes cell migration by inducing matrix metalloproteinase-3
Feng-Ling Yu1, Hung-Jen Liu, Jeng-Woei Lee
1Department of Veterinary Medicine, National Pingtung University of Science and Technology, Pingtung, Taiwan, ROC.
Background/Aims:
Hepatitis B virus (HBV), a major causative agent of hepatocellular carcinoma (HCC), encodes an oncogenic X protein (HBx) that transcriptionally activates multiple viral and cellular promoters. How this regulation influences HCC is unclear.
Methods:
Global gene expression in HBx-expressing and non-expressing hepatoma cells was analyzed using cDNA microarrays.
Results:
Genes that were markedly up- or down-regulated in the presence of HBx included those involved in signal transduction, metabolism, apoptosis, cytokine production, cell cycle, cell adhesion and oncogenesis. Other genes of ill-defined function were also affected. Trans-activation proficient HBx up-regulated the transcription, translation and secretion of matrix metalloproteinase-3 (MMP-3), manifest as a cell migratory phenotype. This HBx effect was abrogated in the presence of a MMP-3 specific peptide inhibitor.
Conclusions:
HBx exerts selective transcriptional control in hepatoma cells and induces cellular migration through the activation of MMP-3.
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