Original Paper

Apoptosis

, Volume 13, Issue 9, pp 1135-1147

Downregulation of hepatoma-derived growth factor activates the Bad-mediated apoptotic pathway in human cancer cells

  • Tsun Yee TsangAffiliated withDepartment of Biochemistry, The Chinese University of Hong Kong
  • , Wan Yee TangAffiliated withDepartment of Biochemistry, The Chinese University of Hong KongDepartment of Environmental Health, University of Cincinnati Medical Center
  • , Wing Pui TsangAffiliated withDepartment of Biochemistry, The Chinese University of Hong Kong
  • , Ngai Na CoAffiliated withDepartment of Biochemistry, The Chinese University of Hong Kong
  • , Siu Kai KongAffiliated withDepartment of Biochemistry, The Chinese University of Hong Kong
  • , Tim Tak KwokAffiliated withDepartment of Biochemistry, The Chinese University of Hong Kong Email author 

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Abstract

Hepatoma-derived growth factor (HDGF) is highly expressed in human cancer and its expression is correlated with poor prognosis of cancer. The growth factor is known to stimulate cell growth while the underlying mechanism is however not clear. Transfection with HDGF cDNA stimulated while its specific antisense oligonucleotides repressed the growth of human hepatocellular carcinoma HepG2 cells. Furthermore, knock-down of HDGF by antisense oligos also induced apoptosis in HepG2 cells and in other human cancer cells, e.g. human squamous carcinoma A431 cells. HDGF knock-down was found to induce the expression of the pro-apoptotic protein Bad and also inactivate ERK and Akt, which in turn led to dephosphorylation of Bad at Ser-112, Ser-136, and activation of the intrinsic apoptotic pathway, i.e. depolarization of the mitochondrial membrane, release of mitochondrial cytochrome c, increase in the processing of caspase 9 and 3. As HDGF knock-down not only suppresses the growth but also induces apoptosis in human cancer cells, HDGF may therefore serve as a survival factor for human cancer cells and a potential target for cancer therapy.

Keywords

HDGF Apoptosis Bad