TGF-beta1/SMAD signaling pathway mediates p53-dependent apoptosis in hepatoma cell lines.
OBJECTIVE
To determine whether transforming growth factor betal (TGF-beta1)/Smad signaling pathway mediates p53-dependent apoptosis in hepatoma cell lines.


METHODS
Three human hepatic carcinoma cell lines, HepG2, Huh-7, and Hep3B, were used in this study. TGF-beta1-induced apoptosis in hepatic carcinoma cell lines was analyzed using TUNEL assay. For identifying the mechanism of apoptosis induced by TGF-beta1, cell lines were transfected with a TGF-beta1-inducible luciferase reportor plasmid containing Smad4 binding elements. After transfection, cells were treated with TGF-beta1, then assayed for luciferase activity.


RESULTS
The apoptosis rate of HepG2 cell lines (48.51% +/- 8.21%) was significantly higher than control (12.72% +/- 2.18%, P <0.05). But TGF-beta1 was not able to induce apoptosis of Huh-7 and Hep3B cell lines. The relative luciferase activity of TGF-beta1-treated HepG2 cell lines (4.38) was significantly higher than control (1.00, P < 0.05). But the relative luciferase activity of TGF-beta1-treated Huh-7 and Hep3B cell lines less increased compared with control.


CONCLUSIONS
HepG2 cells seem to be highly susceptible to TGF-beta1-induced apoptosis compared with Hep3B and Huh-7 cell lines. Smad4 is a central mediator of TGF-beta1 signaling transdution pathway. TGF-beta1/Smad signaling pathway might mediate p53-dependent apoptosis in hepatoma cell lines.
Wang
Chun-lei
CL
Department of General Surgery, the First Hospital, Peking University, Beijing 100034. wangchunlei301@yahoo.com
Wan
Yuan-lian
YL
Liu
Yu-cun
YC
Huang
Zhi-qiang
ZQ
D017209:Apoptosis / Q000187:drug effects*; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D017930:Genes, Reporter; D016158:Genes, p53; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D008156:Luciferases / Q000378:metabolism; D010957:Plasmids; D015398:Signal Transduction; D051901:Smad4 Protein / Q000378:metabolism*; D014162:Transfection; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology*
D051901:Smad4 Protein; D053773:Transforming Growth Factor beta1; D008156:Luciferases