title: Apoptosis of human hepatoma cell lines induced by transforming growth factor beta 1 (TGF-beta1) correlates with p53 and Smad4 activation.
abstract: OBJECTIVE
  To determine the relationships between apoptosis induced by transforming growth factor beta 1(TGF-beta1) and Smad in human hepatoma cell lines.
  
  
  METHODS
  Three human hepatic carcinoma cell lines, involving different status of the p53 gene respectively, were used in this study. TGF-beta1-induced apoptosis in hepatic carcinoma cell lines was quantitated using the terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay. For identification of the mechanism of apoptosis induced by TGF-beta1, these cell lines were transfected with a TGF-beta1-inducible luciferase reporter plasmid containing Smad binding elements (SBE) and luciferase gene using LF2000, then were treated with TGF-beta1. Relative luciferase activity was assayed respectively.
  
  
  RESULTS
  Among three cell lines studied with TUNEL assay, addition of TGF-beta1 induced apoptosis only in HepG2 cells (wild type p53). In contrast, Huh-7 (mutant p53) and Hep3B (deleted p53) cell lines lacked apoptosis. The detection of luciferase activity indicated that HepG2 cells dramatically increased the response to TGF-beta1 induction, Huh-7 and Hep3B cell lines significantly lowered luciferase expression.
  
  
  CONCLUSIONS
  HepG2 cells were highly susceptible to TGF-beta1-induced apoptosis compared with Hep3B and Huh-7 cell lines. Smad4 may be a central mediator of the TGF-beta1 signaling transduction pathway.
authors.affiliation: Department of General Surgery, Peking University First Hospital, Beijing 100034, China. wangchunlei301@yahoo.com
authors.forename: Chun-lei
authors.initials: CL
authors.lastname: Wang
authors.forename: Yuan-lian
authors.initials: YL
authors.lastname: Wan
authors.forename: Yu-cun
authors.initials: YC
authors.lastname: Liu
authors.forename: Zhi-qiang
authors.initials: ZQ
authors.lastname: Huang
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D006528:Carcinoma, Hepatocellular / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D056945:Hep G2 Cells; D006801:Humans; D015398:Signal Transduction / Q000187:drug effects; D051901:Smad4 Protein / Q000378:metabolism*; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
chemical_list: C497796:SMAD4 protein, human; D051901:Smad4 Protein; C495901:TP53 protein, human; D053773:Transforming Growth Factor beta1; D016159:Tumor Suppressor Protein p53