Abstract
Objective:
To study the expressions and activities of Rho GTPases in hypoxia and its relationship with tumor angiogenesis.
Methods:
Three tumor cell lines were used in this study: gastric cancer cell lines AGS, SGC7901 and hepatocellular carcinoma cell line HepG2. Expression level of Rac1 mRNA was detected by semi-quantitative RT-PCR. Activity of Rac1 was determined by pull-down assay and expression of HIF-1alpha, VEGF, p53 and PTEN protein was detected by Westernblot.
Results:
The expression level of Rac1 mRNA was significantly increased in hypoxia compared to normoxia. Pull-down assay showed that hypoxia-induced activity of Rac1 was elevated in a time-dependent manner and climaxed at 3 hours. The expressions of HIF-1alpha and VEGF protein were up-regulated, while those of PTEN and p53 protein were down-regulated.
Conclusion:
These results indicate that hypoxia enhances Rac1 expression which might be involved in tumor angiogenesis by reacting with hypoxia-responsive genes.
Publication types
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English Abstract
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Research Support, Non-U.S. Gov't
MeSH terms
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Cell Hypoxia
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Cell Line, Tumor
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Hepatoblastoma / blood supply
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Hepatoblastoma / metabolism*
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Hepatoblastoma / pathology
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Humans
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Hypoxia-Inducible Factor 1, alpha Subunit / biosynthesis
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Hypoxia-Inducible Factor 1, alpha Subunit / genetics
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Liver Neoplasms / blood supply
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Liver Neoplasms / metabolism*
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Liver Neoplasms / pathology
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Neovascularization, Pathologic*
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PTEN Phosphohydrolase / biosynthesis
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PTEN Phosphohydrolase / genetics
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RNA, Messenger / biosynthesis
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RNA, Messenger / genetics
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Stomach Neoplasms / blood supply
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Stomach Neoplasms / metabolism*
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Stomach Neoplasms / pathology
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Tumor Suppressor Protein p53 / biosynthesis
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Tumor Suppressor Protein p53 / genetics
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Vascular Endothelial Growth Factor A / biosynthesis
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Vascular Endothelial Growth Factor A / genetics
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rac1 GTP-Binding Protein / biosynthesis*
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rac1 GTP-Binding Protein / genetics
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rho GTP-Binding Proteins / biosynthesis*
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rho GTP-Binding Proteins / genetics
Substances
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HIF1A protein, human
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Hypoxia-Inducible Factor 1, alpha Subunit
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RNA, Messenger
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Tumor Suppressor Protein p53
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Vascular Endothelial Growth Factor A
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PTEN Phosphohydrolase
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rac1 GTP-Binding Protein
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rho GTP-Binding Proteins