Histone deacetylases induce angiogenesis by negative regulation of tumor suppressor genes - PubMed (original) (raw)
H J Kwon, Y M Lee, J H Baek, J E Jang, S W Lee, E J Moon, H S Kim, S K Lee, H Y Chung, C W Kim, K W Kim
Affiliations
- PMID: 11283670
- DOI: 10.1038/86507
Histone deacetylases induce angiogenesis by negative regulation of tumor suppressor genes
M S Kim et al. Nat Med. 2001 Apr.
Abstract
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.
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