Studies on the Mechanism of Hypoxic Increase of VEGF Expression in the Hep3B Human Hepatoma Cells.
- Author:
Yoo Wook KWON
1
;
Soo Kyung BAE
;
Jung Ae KIM
;
Kyu Won KIM
;
Byung Chae PARK
Author Information
1. Department of Molecular Biology, Pusan National University, Pusan 609-735, Korea.
- Publication Type:Original Article
- Keywords:
Hypoxia;
Hep3B cell;
VEGF;
Calcium;
c-jun
- MeSH:
Anoxia;
Blotting, Northern;
Calcium;
Carcinoma, Hepatocellular*;
Cell Line;
Cell Survival;
Cytosol;
Humans*;
Transcription Factor AP-1;
Vascular Endothelial Growth Factor A*
- From:Journal of the Korean Cancer Association
1997;29(2):220-226
- CountryRepublic of Korea
- Language:Korean
-
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.
