NDLI: Hepatocyte growth factor induced up-regulations of VEGF through Egr-1 in hepatocellular carcinoma cells

Content Provider	Springer Nature Link
Author	Lee, Kyung Hee Kim, Jae Ryong
Copyright Year	2009
Abstract	The potential role of hepatocyte growth factor (HGF) in the regulation of angiogenesis factors in hepatoma cells is not widely appreciated. We investigated the role of HGF-induced activation of a transcription factor, Egr-1, in the expression of pro-angiogenic factors. Genes associated with angiogenesis induced by HGF were screened by using cDNA microarray technology in hepatocellular carcinoma cell lines, HepG2 and Hep3B. Expression levels of Egr-1, vascular endothelial growth factor (VEGF), and interleukin (IL)-8 were further confirmed by real time RT-PCR and Western blot analysis. Roles of Egr-1 in the levels of HGF-induced up-regulations of VEGF and IL-8 were measured by knockdown of Egr-1 with Egr-1 shRNA and chromatin immunoprecipitation assay. The levels of Egr-1, VEGF and IL-8 were up-regulated in cells treated with HGF. HGF-induced up-regulations of Egr-1, VEGF, and IL-8 were inhibited by the pretreatment with an MEK inhibitor, PD098059. HGF-induced up-regulation of VEGF and IL-8 were repressed by Egr-1 knockdown. HGF enhanced the binding activity of Egr-1 to the VEGF promoter in control cells, but not in the Egr-1-shRNA cells. No constitutive and inducible Egr-1 binding activities to the IL-8 promoter were observed in control and Egr-1-shRNA cells. Egr-1 knockdown reduced the luciferase activities increased by HGF not in the IL-8 promoter, but in the VEGF promoter. Egr-1 might play an important role in the up-regulation of VEGF and IL-8 induced by HGF and contribute to HGF-mediated angiogenesis, which might be promising targets for hepatocellular carcinoma therapy.
Starting Page	685
Ending Page	692
Page Count	8
File Format	PDF
ISSN	02620898
Journal	Clinical & Experimental Metastasis
Volume Number	26
Issue Number	7
e-ISSN	15737276
Language	English
Publisher	Springer Netherlands
Publisher Date	2009-06-13
Publisher Place	Dordrecht
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	HGF Egr-1 VEGF IL-8 Angiogenesis Surgical Oncology Hematology Oncology Biomedicine general Cancer Research
Content Type	Text
Resource Type	Article
Subject	Cancer Research Oncology

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