title: Hepatoma-derived growth factor regulates the bad-mediated apoptotic pathway and induction of vascular endothelial growth factor in stomach cancer cells.
abstract: Hepatoma-derived growth factor (HDGF) is highly expressed in tumor cells and may play an important role in the development and progression of carcinomas. However, the molecular mechanism by which HDGF participates in gastric carcinomatosis requires further analysis. In this study, we determined the role of HDGF in tumorigenesis and elucidated the mechanisms of action. To determine aggressive biological behavior, we knocked down HDGF expression with HDGF-specific shRNA in two gastric cancer cell lines. First, using cDNA microarrary, we showed that hepatocyte growth factor (HGF) induced HDGF and confirmed this by Western blotting. HGF increased HDGF in a dose-dependent manner. We also determined whether HDGF induces angiogenic factor, and found the vascular endothelial growth factor (VEGF) was induced by HDGF. Downregulation of HDGF resulted in a decrement of VEGF. HDGF knock-down was found to induce the expression of the proapoptotic protein, Bad, and also inactivate ERK, which in turn led to dephosphorylation of Bad at ser112 and ser136, and induced apoptosis. Transfection with HDGF-siRNA resulted in a decrement of cell proliferation, as determined with a MMT assay. In an in vitro invasion assay, significantly fewer cells transfected with HDGF-siRNA than control cells were able to invade across a Matrigel membrane barrier. Our results suggest that HDGF is involved in cell growth, cell invasion, and apoptosis. These qualities may contribute to the HDGF-associated aggressive biological behavior of gastric cancer and thus serve as a potential target for cancer therapy.
authors.affiliation: Department of Hematology-Oncology, College of Medicine, Yeungnam University, Daegu, Korea.
authors.forename: Kyung Hee
authors.initials: KH
authors.lastname: Lee
authors.forename: Eun Young
authors.initials: EY
authors.lastname: Choi
authors.forename: Min Kyoung
authors.initials: MK
authors.lastname: Kim
authors.forename: Si Hyung
authors.initials: SH
authors.lastname: Lee
authors.forename: Byung Ik
authors.initials: BI
authors.lastname: Jang
authors.forename: Tae Nyeun
authors.initials: TN
authors.lastname: Kim
authors.forename: Se Won
authors.initials: SW
authors.lastname: Kim
authors.forename: Sang Woon
authors.initials: SW
authors.lastname: Kim
authors.forename: Sun Kyo
authors.initials: SK
authors.lastname: Song
authors.forename: Jae-Ryong
authors.initials: JR
authors.lastname: Kim
authors.forename: Bo Chan
authors.initials: BC
authors.lastname: Jung
mesh_terms: D017209:Apoptosis; D045744:Cell Line, Tumor; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D017228:Hepatocyte Growth Factor / Q000494:pharmacology; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000502:physiology*; D020411:Oligonucleotide Array Sequence Analysis; D010766:Phosphorylation; D013274:Stomach Neoplasms / Q000209:etiology / Q000473:pathology* / Q000628:therapy; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis*; D051025:bcl-Associated Death Protein / Q000502:physiology*
chemical_list: C494819:BAD protein, human; D036341:Intercellular Signaling Peptides and Proteins; D042461:Vascular Endothelial Growth Factor A; D051025:bcl-Associated Death Protein; C051610:hepatoma-derived growth factor; D017228:Hepatocyte Growth Factor; D048049:Extracellular Signal-Regulated MAP Kinases