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- Title
Histone deacetylases induce angiogenesis by negative regulation of tumor suppressor genes.
- Authors
Kim, Myoung Sook; Kwon, Ho Jeong; Lee, You Mie; Baek, Jin Hyen; Jang, Jae-Eun; Lee, Sae-Won; Moon, Eun-Joung; Kim, Hae-Sun; Lee, Seok-Ki; Chung, Hae Young; Kim, Chul Woo; Kim, Kyu-Won
- 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-1α 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.
- Subjects
NEOVASCULARIZATION; HISTONE deacetylase; HYPOXEMIA
- Publication
Nature Medicine, 2001, Vol 7, Issue 4, p437
- ISSN
1078-8956
- Publication type
Article
- DOI
10.1038/86507