Transforming growth factor beta can mediate apoptosis via the expression of TRAIL in human hepatoma cells.
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.
Herzer
Kerstin
K
Division of Immunogenetics, German Cancer Research Center, Heidelberg.
Ganten
Tom M
TM
Schulze-Bergkamen
Henning
H
Grosse-Wilde
Anne
A
Koschny
Ronald
R
Krammer
Peter H
PH
Walczak
Henning
H
D017209:Apoptosis / Q000502:physiology*; D051017:Apoptosis Regulatory Proteins; D006528:Carcinoma, Hepatocellular / Q000503:physiopathology*; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D022781:Hepatocytes / Q000502:physiology; D006801:Humans; D008113:Liver Neoplasms / Q000503:physiopathology*; D008562:Membrane Glycoproteins / Q000096:biosynthesis*; D053221:TNF-Related Apoptosis-Inducing Ligand; D016212:Transforming Growth Factor beta / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*
D051017:Apoptosis Regulatory Proteins; D008562:Membrane Glycoproteins; D053221:TNF-Related Apoptosis-Inducing Ligand; C505653:TNFSF10 protein, human; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha