J Korean Cancer Assoc.  1997 Apr;29(2):220-226.

Studies on the Mechanism of Hypoxic Increase of VEGF Expression in the Hep3B Human Hepatoma Cells

Affiliations
  • 1Department of Molecular Biology, Pusan National University, Pusan 609-735, Korea.
  • 2Department of Internal Medicine, School of Medicine, Kosin University, Pusan 602-030, Korea.

Abstract

PURPOSE: Hepatocellular carcinoma (HCC), a typical hypervasculized tumor is very sensitive to hypoxia and vascular endothelial growth factor (VEGF) has previously been identified to be up-regulated in response to hypoxia in several cell types. However, the molecular mechanisms by which hypoxia is sensed by the cells remain enigmatic. To investigate whether calcium and AP-1 are involved in hypoxia-sensing mechanism, we performed following experiments.
MATERIALS AND METHODS
Hep3B cells were grown in hypoxic condition. To assess cell viability, MTT assay was performed. To investigate the effect of calcium and AP-1, northern blot analysis was performed after treatment with BAPTA/AM.
RESULTS
The expression of VEGF was significantly up-regulated by hypoxia in Hep3B, hepatocellular carcinoma cell line. The increased expression of VEGF induced by hypoxia was blocked by the addition of BAPTA/AM, a cytosolic calcium chelator to the media. In addition, we found that the expression of c-jun protooncogene was also up-regulated by hypoxia. Hypoxic increase of c-jun expression was also normalized by the treatment with BAPTA/AM.
CONCLUSION
These results suggest that the increased expression of VEGF by hypoxia is mediated through the calcium and c-jun signalling pathway in the Hep3B human hepatoma cell lines.

Keyword

Hypoxia; Hep3B cell; VEGF; Calcium; c-jun

MeSH Terms

Anoxia
Blotting, Northern
Calcium
Carcinoma, Hepatocellular*
Cell Line
Cell Survival
Cytosol
Humans*
Transcription Factor AP-1
Vascular Endothelial Growth Factor A*
Calcium
Transcription Factor AP-1
Vascular Endothelial Growth Factor A
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