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

Tsun Yee Tsang, Wan Yee Tang, Wing Pui Tsang, Ngai Na Co, Siu Kai Kong, Tim Tak Kwok

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)1135-1147
Number of pages13
JournalApoptosis
Volume13
Issue number9
DOIs
StatePublished - Sep 1 2008
Externally publishedYes

Keywords

  • Apoptosis
  • Bad
  • HDGF

ASJC Scopus subject areas

  • Pharmacology
  • Pharmaceutical Science
  • Clinical Biochemistry
  • Cell Biology
  • Biochemistry, medical
  • Cancer Research

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