Hepatoma-Derived Growth Factor Regulates the Bad-Mediated Apoptotic Pathway and Induction of Vascular Endothelial Growth Factor in Stomach Cancer Cells

Title
Hepatoma-Derived Growth Factor Regulates the Bad-Mediated Apoptotic Pathway and Induction of Vascular Endothelial Growth Factor in Stomach Cancer Cells
Author(s)
이시형이경희최은영[최은영]김민경장병익김태년김세원김상운송선교김재룡정보찬
Keywords
PROGNOSTIC-FACTOR; LUNG-CANCER; EXPRESSION; PROLIFERATION; CARCINOMA; ACTIVATION
Issue Date
201011
Publisher
COGNIZANT COMMUNICATION CORP
Citation
ONCOLOGY RESEARCH, v.19, no.2, pp.67 - 76
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 ser(112) and ser(136), 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.
URI
http://hdl.handle.net/YU.REPOSITORY/23413http://dx.doi.org/10.3727/096504010X12864748215043
ISSN
0965-0407
Appears in Collections:
의과대학 > 내과학교실 > Articles
의과대학 > 성형외과학교실 > Articles
의과대학 > 생화학.분자생물학교실 > Articles
의과대학 > 진단검사의학교실 > Articles
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