Hepatocyte Growth Factor-Mediated Gastrin-Releasing Peptide Induces IL-8 Expression Through Ets-1 in Gastric Cancer Cells

Title
Hepatocyte Growth Factor-Mediated Gastrin-Releasing Peptide Induces IL-8 Expression Through Ets-1 in Gastric Cancer Cells
Author(s)
이경희고성애김재룡
Keywords
NF-KAPPA-B; INTERLEUKIN-8 EXPRESSION; PLASMINOGEN-ACTIVATOR; CLINICAL-IMPLICATIONS; HUMAN HEAD; CARCINOMA; C-ETS-1; ANGIOGENESIS; ANTAGONISTS; RECEPTORS
Issue Date
201306
Publisher
COGNIZANT COMMUNICATION CORP
Citation
ONCOLOGY RESEARCH, v.20, no.9, pp.393 - 402
Abstract
Gastric cancer cells secrete a variety of proangiogenic molecules, including IL-8 and VEGF. However, factors regulating the expression of proangiogenic genes for gastric cancer remain largely undefined. We investigated the role of HGF-induced activation of GRP and Ets-1 transcription factor in expression of the proangiogenic factor IL-8. The genes associated with angiogenesis induced by HGF were screened using cDNA micro-array technology in two gastric cancer cell lines (NUGC-3 and MKN-28). First, GRP RNA and protein were confirmed to be upregulated. Then, expression of GRP, Ets-1, and IL-8 were further estimated by Western blot analysis. A role for Ets-1 in HGF-induced upregulation of IL-8 was determined by knockdown of Ets-1 with Ets-1 sh-RNA and a chromatin immune precipitation assay. The levels of GRP, Ets-1, and IL-8 were upregulated in cells treated with HGF in a dose-dependent manner. HGF-induced expression of Ets-1 and IL-8 was increased more by GRP treatment and inhibited by pretreatment with an ERK 1/2 inhibitor (PD098059). HGF-induced upregulation of IL-8 was repressed by Ets-1 knockdown. HGF enhanced the binding activity of Ets-1 to the IL-8 promoter in control cells, but not in the Ets-1 shRNA cells. We confirmed the functional role of HGF-induced Ets-1 in activation of the IL-8 promoter by the reporter gene assay. Downregulation of IL-8 also decreased in vitro cell invasion. In conclusion, HGF mediated the GRP induction of IL-8 expression through Ets-1, which thus might serve as a promising target for gastric cancer therapy.
URI
http://hdl.handle.net/YU.REPOSITORY/29841http://dx.doi.org/10.3727/096504013X13657689382770
ISSN
0965-0407
Appears in Collections:
의과대학 > 내과학교실 > Articles
의과대학 > 생화학.분자생물학교실 > Articles
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