Histone deacetylases induce angiogenesis by negative regulation of tumor suppressor genes.

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.

journal_name

Nat Med

journal_title

Nature medicine

authors

Kim MS,Kwon HJ,Lee YM,Baek JH,Jang JE,Lee SW,Moon EJ,Kim HS,Lee SK,Chung HY,Kim CW,Kim KW

doi

10.1038/86507

keywords:

subject

Has Abstract

pub_date

2001-04-01 00:00:00

pages

437-43

issue

4

eissn

1078-8956

issn

1546-170X

pii

86507

journal_volume

7

pub_type

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