Vanadate-Induced Expression of Hypoxia-Inducible Factor 1alpha and Vascular Endothelial Growth Factor Through Phosphatidylinositol 3-Kinase/Akt Pathway and Reactive Oxygen Species

Details

• Personal Author:
  Ding M ; Gao N ; Jiang BH ; Leonard, Stephen S. ; Liu KJ ; Shi X ; Zhang Z ; Zheng JZ
• Description:
  Hypoxia-inducible factor 1 (HIF-1) is a heterodimeric basic helix-loop-helix transcription factor composed of HIF-1alpha and HIF-1 beta/aryl hydrocarbon nuclear translocator subunits. HIF-1 expression is induced by hypoxia, growth factors, and activation of oncogenes. In response to hypoxia, HIF-1 activates the expression of many genes including vascular endothelial growth factor (VEGF) and erythropoietin. HIF-1 and VEGF play an important role in angiogenesis and tumor progression. Vanadate is widely used in industry, and is a potent inducer of tumors in humans and animals. In this study, we demonstrate that vanadate induces HIF-1 activity through the expression of HIF-1alpha but not HIF-1beta subunit, and increases VEGF expression in DU145 human prostate carcinoma cells. We also studied the signaling pathway involved in vanadate-induced HIF-1 alpha and VEGF expression and found that phosphatidylinositol 3-kinase/Akt signaling was required for HIF-1 and VEGF expression induced by vanadate, whereas mitogen-activated protein kinase pathway was not required. We also found that reactive oxygen species (ROS) were involved in vanadate-induced expression of HIF-1 and VEGF in DU145 cells. The major species of ROS responsible for the induction of HIF-1 and VEGF expression was H2O2. These results suggest that the expression of HIF-1 and VEGF induced by vanadate through PI3K/Akt may be an important signaling pathway in the vanadate-induced carcinogenesis, and ROS may play an important role. [Description provided by NIOSH]
• Subjects:
  Biochemistry Carcinogens Chemistry Genetics Lung Lung Diseases Neoplasms Occupational Health Respiratory System Respiratory Tract Diseases Safety Vanadium Compounds

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• Keywords:
  Biochemical-analysis Biochemical-tests Cancer Carcinomas Cell-biology Cell-growth Cellular-function Chemical-kinetics Chemical-properties Chemical-reactions Gene-mutation Genes Genotoxic-effects Humans Hypoxia Mutation Tumors Vanadium-compounds

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• ISSN:
  0021-9258
• Document Type:
  Text
• Genre:
  Journal Article
• Place as Subject:
  OSHA Region 3 ; West Virginia
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Division:
  HELD - Health Effects Laboratory Division
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  277
• Issue:
  30
• NIOSHTIC Number:
  nn:20022383
• Citation:
  J Biol Chem 2002 Aug; 277(30):31963-31971
• Contact Point Address:
  Mary Babb Randolph Cancer Center, Department of Microbiology, Immunology and Cell Biology, West Virginia University, Morgantown, West Virginia 26506-9300, USA
• Email:
  bhjiang@hsc.wvu.edu
• Federal Fiscal Year:
  2002
• NORA Priority Area:
  Research Tools and Approaches: Cancer Research Methods
• Peer Reviewed:
  True
• Source Full Name:
  Journal of Biological Chemistry
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:8948afe115ff298e8e1abf033175eaddf224d0e9a963a9f2db4d9623c72934f29bf959c11acd3ad528659ad993d3457180d0c2d2116fb5a9e4c723f0a97818c2
• Download URL:
  https://stacks.cdc.gov/view/cdc/199180/cdc_199180_DS1.pdf
• File Type:
  [PDF - 526.90 KB ]