Abstract
Since hypoxia has been considered to enhance metastatic potential in solid tumors via a neo-angiogenesis caused by vascular endothelial cell growth factors (VEGFs) induced by hypoxia inducible factor-1alpha (HIF-1alpha), the effects of hypoxia on human seminoma cell lines were examined in terms of growth, morphology, gene expression, protein expression and cell cycle perturbation. Growth was inhibited in long-term cultures with morphological changes to the spindle form. The gene expression of VEGF-C was markedly enhanced and the production of VEGF-A increased during hypoxia, although HIF-1alpha was not upregulated at the protein or message level. Hypoxic culture caused G1 cell cycle arrest with upregulation of the p15/ink4b and p27/Kip1 genes, whereas no increase of apoptotic cells was observed on up-regulation of the heat shock protein (HSP) 70 gene. The adhesion molecules were only slightly altered.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Apoptosis
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Cell Adhesion
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Cell Cycle Proteins / metabolism
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Cell Division
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Cyclin-Dependent Kinase Inhibitor p15
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Cyclin-Dependent Kinase Inhibitor p16 / metabolism
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Cyclin-Dependent Kinase Inhibitor p27
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DNA, Complementary / metabolism
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Endothelial Growth Factors / biosynthesis
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Flow Cytometry
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G1 Phase
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HSP70 Heat-Shock Proteins / metabolism
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Humans
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Hyaluronan Receptors / biosynthesis
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Hypoxia*
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Immunohistochemistry
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Intercellular Adhesion Molecule-1 / biosynthesis
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Lymphatic Metastasis
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Male
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RNA / metabolism
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Reverse Transcriptase Polymerase Chain Reaction
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Seminoma / metabolism*
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Seminoma / pathology
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Testicular Neoplasms / metabolism*
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Testicular Neoplasms / pathology
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Time Factors
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Tumor Cells, Cultured
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Tumor Suppressor Proteins / metabolism
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Up-Regulation*
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Vascular Endothelial Growth Factor A
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Vascular Endothelial Growth Factor C
Substances
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CDKN2B protein, human
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Cell Cycle Proteins
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Cyclin-Dependent Kinase Inhibitor p15
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Cyclin-Dependent Kinase Inhibitor p16
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DNA, Complementary
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Endothelial Growth Factors
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HSP70 Heat-Shock Proteins
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Hyaluronan Receptors
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Tumor Suppressor Proteins
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Vascular Endothelial Growth Factor A
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Vascular Endothelial Growth Factor C
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Intercellular Adhesion Molecule-1
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Cyclin-Dependent Kinase Inhibitor p27
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RNA