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

Research output: Journal Publications and Reviews (RGC: 21, 22, 62)21_Publication in refereed journal

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Author(s)

  • Lei Jiang
  • Yiu-Kay Lai
  • Jin-Fang Zhang
  • Chu-Yan Chan
  • Gang Lu
  • Marie C.M. Lin
  • Ji-Cheng Li
  • Hsiang-Fu Kung

Detail(s)

Original languageEnglish
Pages (from-to)2035-2042
Journal / PublicationWorld Journal of Gastroenterology
Volume18
Issue number17
Publication statusPublished - 7 May 2012
Externally publishedYes

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. © 2012 Baishideng. All rights reserved.

Research Area(s)

  • Growth inhibition, Hepatocellular carcinoma, Stathmin, Transforming growth factorβ, Transforming growth factor-β-inducible early gene 1

Citation Format(s)

Transactivation of the TIEG1 confers growth inhibition of transforming growth factor-β-susceptible hepatocellular carcinoma cells. / Jiang, Lei; Lai, Yiu-Kay; Zhang, Jin-Fang; Chan, Chu-Yan; Lu, Gang; Lin, Marie C.M.; He, Ming-Liang; Li, Ji-Cheng; Kung, Hsiang-Fu.

In: World Journal of Gastroenterology, Vol. 18, No. 17, 07.05.2012, p. 2035-2042.

Research output: Journal Publications and Reviews (RGC: 21, 22, 62)21_Publication in refereed journal