Abstract
Recent work has indicated that oxygen-sensing mechanism(s) resembling those controlling erythropoietin production operate in many non-erythropoietin-producing cells. To pursue the implication that such a system might control other genes, we studied oxygen-regulated expression of mRNAs for vascular endothelial growth factor, platelet-derived growth factor (PDGF) A and B chains, placental growth factor (PLGF), and transforming growth factor in four different cell lines and compared the characteristics with those of erythropoietin regulation. Oxygen-regulated expression was demonstrated for each gene in at least one cell type. However, the response to hypoxia (1% oxygen) varied markedly, ranging from a 13-fold increase (PDGF-B in Hep G2 cells) to a 2-fold decrease (PLGF in the trophoblastic line BeWo). For each gene/cell combination, both the magnitude and direction of the response to hypoxia were mimicked by exposure to cobaltous ions or two different iron-chelating agents, desferrioxamine and hydroxypyridinones. These similarities with established characteristics of erythropoietin regulation indicate that a similar mechanism of oxygen sensing is operating on a variety of vascular growth factors, and they suggest that chelatable iron is closely involved in the mechanism.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
MeSH terms
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Angiogenesis Inducing Agents / biosynthesis
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Carcinoma, Hepatocellular
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Cell Hypoxia
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Cell Line
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Chelating Agents / pharmacology*
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Cobalt / pharmacology*
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Deferoxamine / pharmacology*
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Endothelial Growth Factors / biosynthesis
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Erythropoietin / biosynthesis
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Gene Expression Regulation, Neoplastic / drug effects*
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Growth Substances / biosynthesis*
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Humans
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Liver Neoplasms
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Lymphokines / biosynthesis
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Molecular Sequence Data
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Neovascularization, Pathologic*
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Placenta Growth Factor
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Platelet-Derived Growth Factor / biosynthesis
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Pregnancy Proteins / biosynthesis
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RNA, Messenger / biosynthesis
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RNA, Small Nuclear / biosynthesis
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Transforming Growth Factor beta / biosynthesis
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Tumor Cells, Cultured
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Vascular Endothelial Growth Factor A
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Vascular Endothelial Growth Factors
Substances
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Angiogenesis Inducing Agents
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Chelating Agents
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Endothelial Growth Factors
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Growth Substances
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Lymphokines
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PGF protein, human
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Platelet-Derived Growth Factor
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Pregnancy Proteins
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RNA, Messenger
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RNA, Small Nuclear
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Transforming Growth Factor beta
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Vascular Endothelial Growth Factor A
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Vascular Endothelial Growth Factors
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Erythropoietin
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Placenta Growth Factor
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Cobalt
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Deferoxamine
Associated data
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GENBANK/M63971
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GENBANK/X01366
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GENBANK/X02157
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GENBANK/X02811
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GENBANK/X02812
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GENBANK/X03795
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GENBANK/X54936