Histone deacetylases induce angiogenesis by negative regulation of tumor suppressor genes

Myoung Sook Kim, Ho Jeong Kwon, You Mie Lee, Jin Hyen Baek, Jae Eun Jang, Sae Won Lee, Eun Joung Moon, Hae Sun Kim, Seok Ki Lee, Hae Young Chung, Chul Woo Kim, Kyu Won Kim

Research output: Contribution to journalArticlepeer-review

705 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)437-443
Number of pages7
JournalNature Medicine
Issue number4
Publication statusPublished - 2001

Bibliographical note

Funding Information:
Acknowledgments We thank S.L. Schreiber for the gift of pBJ5-wt-HDAC1–expressing vector; J.A. Raleigh for hypoxia marker, pimonidazole and its associated antibody; and B.P. Yu for critical reading of the manuscript. Financial support was from the National Research Laboratory Fund (2000-N-NL-01-C-015), the Ministry of Science and Technology, Korea (to K-W.K.) and the Korea Science and Engineering Foundation (to H.J.K.).

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)


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