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

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

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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.

Growth inhibitionHepatocellular carcinomaStathminTransforming growth factor-βTransforming growth factor-β-inducible early gene 1

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

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Laboratory of Internal Medicine, The First Affiliated Hospital of Wenzhou Medical College, Wenzhou 325000, Zhejiang Province, China

Department of Life Science, National Tsing Hua University, Hsinchu 30013, Taiwan

Stanley Ho Centre for Emerging Infectious Diseases,The Chinese University of Hong Kong, Shatin 999077, Hong Kong, China

Brain Tumor Centre and Division of Neurosurgery, Department of Surgery, The Chinese University of Hong Kong, Shatin 999077, Hong Kong, China

Institute of Cell Biology, Zhejiang University,Hangzhou 310058, Zhejiang Province, China

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Hong Kong Research Grant CouncilHong Kong Research Grant CouncilScientific Research Fund of Zhejiang Provincial Education DepartmentWenzhou Science and Technology Bureau ProgramQianjiang Talents Project of Zhejiang Province

467109467507Y200906317Y201000172011R10058

2012

10.3748/wjg.v18.i17.2035

世界胃肠病学杂志(英文版)
太原消化病研治中心

世界胃肠病学杂志(英文版)

SCI
影响因子：1.001
ISSN：1007-9327
年,卷(期)：2012.18(17)
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