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Updated: Aug 22, 2026

A Simple Bioassay for the Evaluation of Vascular Endothelial Growth Factors
Published on: March 15, 2016
Regulation of vascular endothelial growth factor expression in human gastric cancer cells by interleukin-1beta
Michiya Kawaguchi1, Morihisa Akagi, Mike J Gray
1Department of Cancer Biology, University of Texas M. D. Anderson Cancer Center, Houston, Tex, USA.
Background:
Vascular endothelial growth factor (VEGF), a dominant angiogenic factor in gastric cancer, is upregulated by cytokines in the tumor microenvironment. Interleukin-1beta (IL-1beta), a proinflammatory cytokine, has been shown to be proangiogenic in vivo, despite its not demonstrating angiogenic activity in vitro. We hypothesized that IL-1beta regulates VEGF expression in human gastric cancer cells and investigated the mechanism by which this occurs.
Methods:
We treated the TMK-1 human gastric cancer cell line with IL-1beta for 1 to 24 hours, and then analyzed VEGF mRNA expression by Northern blotting and signaling intermediates by Western blotting. Signaling inhibitors were used to identify the dominant pathways involved in IL-1beta induction of VEGF. VEGF promoter-luciferase constructs and transcription blockers were used to investigate the transcriptional regulation of VEGF by IL-1beta.
Results:
Treating TMK-1 cells with IL-1beta increased VEGF mRNA levels and activated extracellular signal-regulated kinases 1 and 2 (Erk 1/2) and p38, but not Akt. Inhibitors of the Erk and p38 pathways blocked IL-1beta induction of VEGF mRNA. Treating TMK-1 cells with IL-1beta also increased VEGF promoter activity. VEGF transcriptional activity was found to depend on a 120-bp region just proximal to the transcription start site.
Conclusions:
In human gastric cancer cells, IL-1beta induced VEGF through Erk- and p38-dependent pathways; this induction of VEGF was transcriptionally regulated.
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