Nature medicine, 2001-04, Vol.7 (4), p.437-443
2001
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- Autor(en) / Beteiligte
- Titel
- Histone deacetylases induce angiogenesis by negative regulation of tumor suppressor genes
- Ist Teil von
- Nature medicine, 2001-04, Vol.7 (4), p.437-443
- Ort / Verlag
- United States: Nature Publishing Group
- Erscheinungsjahr
- 2001
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- Low oxygen tension influences tumor progression by enhancing angiogenesis; and histone deacetylases (HDAC) are implicated in alteration of chromatin assembly and tumorigenesis. Here we show induction of HDAC under hypoxia and elucidate a role for HDAC in the regulation of hypoxia-induced angiogenesis. Overexpressed wild-type HDAC1 downregulated expression of p53 and von Hippel-Lindau tumor suppressor genes and stimulated angiogenesis of human endothelial cells. A specific HDAC inhibitor, trichostatin A (TSA), upregulated p53 and von Hippel-Lindau expression and downregulated hypoxia-inducible factor-1alpha and vascular endothelial growth factor. TSA also blocked angiogenesis in vitro and in vivo. TSA specifically inhibited hypoxia-induced angiogenesis in the Lewis lung carcinoma model. These results indicate that hypoxia enhances HDAC function and that HDAC is closely involved in angiogenesis through suppression of hypoxia-responsive tumor suppressor genes.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1078-8956eISSN: 1546-170XDOI: 10.1038/86507Titel-ID: cdi_proquest_miscellaneous_77019007
- Format
- –
- Schlagworte
- Angiogenesis, Animals, Cattle, Cell Line, DNA-Binding Proteins - genetics, Endothelial Growth Factors - genetics, Enzyme Inhibitors - pharmacology, Gene Expression Regulation - drug effects, Genes, Genes, p53 - drug effects, Genes, Tumor Suppressor - drug effects, Hippel-Lindau gene, histone deacetylase, Histone Deacetylase Inhibitors, Histone Deacetylases - physiology, Humans, Hydroxamic Acids - pharmacology, Hypoglycemia, Hypoxia, Hypoxia - genetics, Hypoxia - pathology, Hypoxia-Inducible Factor 1, Hypoxia-Inducible Factor 1, alpha Subunit, Lymphokines - genetics, Male, Medicine, Mice, Mice, Inbred C57BL, Neovascularization, Physiologic - drug effects, Neovascularization, Physiologic - genetics, Nuclear Proteins - genetics, Pharmacy, Protein expression, Publishing, Transcription Factors, trichostatin A, Tumorigenesis, Tumors, Vascular endothelial growth factor, Vascular Endothelial Growth Factor A, Vascular Endothelial Growth Factors, VHL gene, von Hippel-Lindau Disease - genetics