AIM: To investigate the role of transforming growth factor (TGF)-β-inducible 
early gene 1 (TIEG1) in TGF-β-induced growth inhibition in hepatocellular 
carcinoma (HCC) cells.
METHODS: Human hepatocyte and HCC cell lines with varied susceptibilities to 
TGF-β1 were tested by methylthiazoletetrazolium (MTT) assay. The expression 
changes of Smad2, Smad3, Smad4, Smad7, TIEG1 and TIEG2 gene following treatment 
with TGF-β1 in a TGF-β-sensitive hepatocyte cell line (MIHA), a TGF-β-sensitive 
hepatoma cell line (Hep3B) and two TGF-β-insensitive hepatoma cell lines (HepG2 
and Bel7404) were examined. SiRNA targeting TIEG1 was transfected into Hep3B 
cells and the sensitivity of cells to TGF-β1 was examined. Overexpression of 
TIEG1 was induced by lentiviral-mediated transduction in TGF-β1-resistant 
hepatoma cell lines (Bel7404 and HepG2). MTT assay and 
4',6-Diamidino-2-phenylindole staining were used to identify cell viability and 
apoptosis, respectively. The expression level of stathmin was measured by 
reverse transcriptase polymerase chain reaction and Western-blotting analysis, 
and stathmin promoter activity by TIEG1 was monitored by a luciferase reporter 
gene system.
RESULTS: TIEG1 was significantly upregulated by TGF-β1 in the TGF-β1-sensitive 
HCC cell line, Hep3B, but not in the resistant cell lines. The suppression of 
TIEG1 by siRNAs decreased the sensitivity of Hep3B cells to TGF-β1, whereas the 
overexpression of TIEG1 mediated growth inhibition and apoptosis in 
TGF-β1-resistant HCC cell lines, which resembled those of TGF-β1-sensitive HCC 
cells treated with TGF-β1. Our data further suggested that stathmin was a direct 
target of TIEG1, as stathmin was significantly downregulated by TIEG1 
overexpression, and stathmin promoter activity was inhibited by TIEG1 in a 
dose-dependent manner.
CONCLUSION: Our data suggest that transactivation of TIEG1 conferred growth 
inhibition of TGF-β-susceptible human HCC cells.