Suppression of tumor growth through disruption of hypoxia-inducible transcription

Nat Med. 2000 Dec;6(12):1335-40. doi: 10.1038/82146.


Chronic hypoxia, a hallmark of many tumors, is associated with angiogenesis and tumor progression. Strategies to treat tumors have been developed in which tumor cells are targeted with drugs or gene-therapy vectors specifically activated under hypoxic conditions. Here we report a different approach, in which the normal transcriptional response to hypoxia is selectively disrupted. Our data indicate that specific blockade of the interaction of hypoxia-inducible factor with the CH1 domain of its p300 and CREB binding protein transcriptional coactivators leads to attenuation of hypoxia-inducible gene expression and diminution of tumor growth. Thus, disrupting the normal co-activational response to hypoxia may be a new and useful therapeutic strategy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Binding Sites
  • CREB-Binding Protein
  • Cell Hypoxia / genetics*
  • DNA-Binding Proteins / metabolism*
  • E1A-Associated p300 Protein
  • Gene Expression Regulation, Neoplastic*
  • Genetic Therapy / methods
  • Hypoxia-Inducible Factor 1
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Mice
  • Mice, Nude
  • Neoplasms, Experimental / therapy*
  • Neovascularization, Pathologic
  • Nuclear Proteins / metabolism*
  • Protein Binding
  • Trans-Activators / metabolism*
  • Transcription Factors*
  • Transcription, Genetic


  • DNA-Binding Proteins
  • Hif1a protein, mouse
  • Hypoxia-Inducible Factor 1
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Nuclear Proteins
  • Trans-Activators
  • Transcription Factors
  • CREB-Binding Protein
  • Crebbp protein, mouse
  • E1A-Associated p300 Protein
  • Ep300 protein, mouse