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

Transforming growth factor β (TGF‐β) has been shown to induce apoptotic cell death in normal and transformed hepatocytes. However, the exact mechanism through which TGF‐β induces cell death is still unknown. We examined a potential role of various death receptor/ligand systems in TGF‐β–induced apoptosis and identified the tumor necrosis factor–related apoptosis‐inducing ligand (TRAIL) as a mediator of TGF‐β–induced apoptosis in hepatoma cells. TGF‐β–induced apoptosis is significantly impaired upon blockage of TRAIL. We show that TRAIL is upregulated in hepatoma cells upon treatment with TGF‐β, whereas TRAIL receptor levels remain unchanged. In conclusion , our results provide evidence that the TRAIL system is critically involved in TGF‐β–induced cell death in liver pathology. (H EPATOLOGY 2005;42:183–192.)