Hepatitis B virus X protein promotes the growth of hepatocellular carcinoma by modulation of the Notch signaling pathway

Oncol Rep. 2012 Apr;27(4):1170-6. doi: 10.3892/or.2012.1620. Epub 2012 Jan 3.

Abstract

Hepatitis B virus X protein (HBx) plays a crucial role in the development of hepatocellular carcinoma (HCC), however, little is known about the mechanism. Here, we investigated the relationship between HBx and Notch signaling in HepG2 cells after they were transfected with the HBx gene. It was found that HBx upregulated the expression of Notch-1, Jagged-1 and Hes-1 at the transcriptional level by binding to the Notch-1 intracellular domain, which is congruent with the observations of enhanced malignant biological activities of HBx-transfected HepG2 cells compared with normal HepG2 cells. However, while Notch signaling was blocked, the HBx-induced abnormalities were partially reversed. These findings suggest that HBx may promote the progression of HCC via the activated Notch pathway.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis
  • Basic Helix-Loop-Helix Transcription Factors / metabolism
  • Calcium-Binding Proteins / metabolism
  • Carcinoma, Hepatocellular / genetics
  • Carcinoma, Hepatocellular / metabolism*
  • Carcinoma, Hepatocellular / pathology
  • Cell Cycle Checkpoints
  • Cell Proliferation* / drug effects
  • Dipeptides / pharmacology
  • Hep G2 Cells
  • Homeodomain Proteins / metabolism
  • Humans
  • Intercellular Signaling Peptides and Proteins / metabolism
  • Jagged-1 Protein
  • Liver Neoplasms / genetics
  • Liver Neoplasms / metabolism*
  • Liver Neoplasms / pathology
  • Membrane Proteins / metabolism
  • Receptor, Notch1 / antagonists & inhibitors
  • Receptor, Notch1 / metabolism*
  • Serrate-Jagged Proteins
  • Signal Transduction* / drug effects
  • Time Factors
  • Trans-Activators / genetics
  • Trans-Activators / metabolism*
  • Transcription Factor HES-1
  • Transfection
  • Viral Regulatory and Accessory Proteins

Substances

  • Basic Helix-Loop-Helix Transcription Factors
  • Calcium-Binding Proteins
  • Dipeptides
  • Homeodomain Proteins
  • Intercellular Signaling Peptides and Proteins
  • JAG1 protein, human
  • Jagged-1 Protein
  • Membrane Proteins
  • N-(N-(3,5-difluorophenacetyl)alanyl)phenylglycine tert-butyl ester
  • NOTCH1 protein, human
  • Receptor, Notch1
  • Serrate-Jagged Proteins
  • Trans-Activators
  • Transcription Factor HES-1
  • Viral Regulatory and Accessory Proteins
  • hepatitis B virus X protein
  • HES1 protein, human