Exp Mol Med.  2009 Jan;41(1):51-58. 10.3858/emm.2009.41.1.007.

Regulation of glucose metabolism-related genes and VEGF by HIF-1alpha and HIF-1beta, but not HIF-2alpha, in gastric cancer

Affiliations
  • 1Genome Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon 305-806, Korea. nskim37@kribb.re.kr
  • 2Department of Pathology, Eulji University School of Medicine, Daejeon 301-746, Korea.
  • 3School of Life Sciences and Biotechnology, College of Natural Sciences, Kyungpook National University Daegu 702-701, Korea.

Abstract

Hypoxia-inducible factors (HIFs) are transcription factors that activate the transcription of target genes involved in crucial aspects of cancer development. This study investigated the expression of HIFs and their contribution to the regulation of target genes related to angiogenesis and glucose metabolism in gastric cancer. The data showed that HIFs were over-expressed in gastric cancer and that activation of the target genes was observed mainly in the early stages. Moreover, the results of the present study revealed that only HIF-1alpha, but not HIF-2alpha dimerizes with HIF-1beta and then regulates expression of target genes in response to hypoxia. The results of the present study demonstrate that HIF-1alpha and HIF-1beta enhances expression of VEGF and glucose metabolism-related genes in response to hypoxia in gastric cancer. These data offer important information regarding HIF pathways in the development of gastric cancer.

Keyword

glucose metabolism disorders; hypoxia-inducible factor 1; neovascularization, pathologic; stomach neoplasms; vascular endothelial growth factor A

MeSH Terms

Aryl Hydrocarbon Receptor Nuclear Translocator/*genetics/metabolism
Basic Helix-Loop-Helix Transcription Factors/*genetics/metabolism
Cell Line, Tumor
Gene Expression Regulation, Neoplastic
Glucose/*metabolism
Humans
Hypoxia-Inducible Factor 1, alpha Subunit/*genetics/metabolism
Neovascularization, Pathologic/genetics/metabolism
Stomach Neoplasms/*genetics/metabolism
Vascular Endothelial Growth Factor A/*genetics/metabolism
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