Transactivation of the TIEG1 confers growth inhibition of transforming growth factor-β-susceptible hepatocellular carcinoma cells.

Abstract

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.

• Authors: Lei Jiang, Yiu-Kay Lai, Jin-Fang Zhang, Chu-Yan Chan, Gang Lu, Marie Cm Lin, Ming-Liang He, Ji-Cheng Li, Hsiang-Fu Kung
• Journal: World journal of gastroenterology (World J Gastroenterol) Vol. 18 Issue 17 Pg. 2035-42 (May 07 2012) ISSN: 2219-2840 [Electronic] United States
• PMID: 22563190 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Early Growth Response Transcription Factors
• KLF10 protein, human
• Kruppel-Like Transcription Factors
• Smad Proteins
• Stathmin
• Transforming Growth Factor beta1

Topics

• Apoptosis (drug effects)
• Carcinoma, Hepatocellular (drug therapy, pathology)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Early Growth Response Transcription Factors (physiology)
• Hepatocytes (drug effects)
• Humans
• Kruppel-Like Transcription Factors (physiology)
• Liver Neoplasms (drug therapy, pathology)
• Promoter Regions, Genetic
• Smad Proteins (metabolism)
• Stathmin (genetics)
• Transcriptional Activation
• Transforming Growth Factor beta1 (pharmacology)