Transforming growth factor beta can mediate apoptosis via the expression of TRAIL in human hepatoma cells

Hepatology. 2005 Jul;42(1):183-92. doi: 10.1002/hep.20757.


Transforming growth factor beta (TGF-beta) has been shown to induce apoptotic cell death in normal and transformed hepatocytes. However, the exact mechanism through which TGF-beta induces cell death is still unknown. We examined a potential role of various death receptor/ligand systems in TGF-beta-induced apoptosis and identified the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) as a mediator of TGF-beta-induced apoptosis in hepatoma cells. TGF-beta-induced apoptosis is significantly impaired upon blockage of TRAIL. We show that TRAIL is upregulated in hepatoma cells upon treatment with TGF-beta, whereas TRAIL receptor levels remain unchanged. In conclusion, our results provide evidence that the TRAIL system is critically involved in TGF-beta-induced cell death in liver pathology.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / physiology*
  • Apoptosis Regulatory Proteins
  • Carcinoma, Hepatocellular / physiopathology*
  • Cell Line, Tumor
  • Cells, Cultured
  • Hepatocytes / physiology
  • Humans
  • Liver Neoplasms / physiopathology*
  • Membrane Glycoproteins / biosynthesis*
  • TNF-Related Apoptosis-Inducing Ligand
  • Transforming Growth Factor beta / physiology*
  • Tumor Necrosis Factor-alpha / biosynthesis*


  • Apoptosis Regulatory Proteins
  • Membrane Glycoproteins
  • TNF-Related Apoptosis-Inducing Ligand
  • TNFSF10 protein, human
  • Transforming Growth Factor beta
  • Tumor Necrosis Factor-alpha