Hepatitis B virus X protein promotes cell migration by inducing matrix metalloproteinase-3.
OBJECTIVE
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.
Yu
Feng-Ling
FL
Department of Veterinary Medicine, National Pingtung University of Science and Technology, Pingtung, Taiwan, ROC.
Liu
Hung-Jen
HJ
Lee
Jeng-Woei
JW
Liao
Ming-Huei
MH
Shih
Wen-Ling
WL
D017209:Apoptosis / Q000502:physiology / Q000528:radiation effects; D006528:Carcinoma, Hepatocellular / Q000378:metabolism / Q000473:pathology / Q000821:virology*; D045744:Cell Line, Tumor; D002465:Cell Movement; D006515:Hepatitis B virus / Q000502:physiology*; D019694:Hepatitis B, Chronic / Q000378:metabolism / Q000473:pathology / Q000821:virology*; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism / Q000473:pathology / Q000821:virology*; D019278:Matrix Metalloproteinase 3 / Q000235:genetics / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D010641:Phenotype; D015534:Trans-Activators / Q000235:genetics* / Q000378:metabolism; D018808:Transcription Factor AP-1 / Q000378:metabolism; D014158:Transcription, Genetic; D014466:Ultraviolet Rays; D054334:Viral Regulatory and Accessory Proteins
D015534:Trans-Activators; D018808:Transcription Factor AP-1; D054334:Viral Regulatory and Accessory Proteins; C057628:hepatitis B virus X protein; D019278:Matrix Metalloproteinase 3