Unknown

Dataset Information

0

Inhibition of vascular endothelial growth factor with a sequence-specific hypoxia response element antagonist.

ABSTRACT: Vascular endothelial growth factor (VEGF) and its receptors have been implicated as key factors in tumor angiogenesis that are up-regulated by hypoxia. We evaluated the effects of DNA-binding small molecules on hypoxia-inducible transcription of VEGF. A synthetic pyrrole-imidazole polyamide designed to bind the hypoxia response element (HRE) was found to disrupt hypoxia-inducible factor (HIF) binding to HRE. In cultured HeLa cells, this resulted in a reduction of VEGF mRNA and secreted protein levels. The observed effects were polyamide-specific and dose-dependent. Analysis of genome-wide effects of the HRE-specific polyamide revealed that a number of hypoxia-inducible genes were down-regulated. Pathway-based regulation of hypoxia-inducible gene expression with DNA-binding small molecules may represent a new approach for targeting angiogenesis.

SUBMITTER: Olenyuk BZ 

PROVIDER: S-EPMC534742 | biostudies-literature | 2004 Nov

REPOSITORIES: biostudies-literature

Json Xml
altmetric image

Publications

Inhibition of vascular endothelial growth factor with a sequence-specific hypoxia response element antagonist.

Olenyuk Bogdan Z BZ   Zhang Guo-Jun GJ   Klco Jeffery M JM   Nickols Nicholas G NG   Kaelin William G WG   Dervan Peter B PB  

Proceedings of the National Academy of Sciences of the United States of America 20041119 48

Vascular endothelial growth factor (VEGF) and its receptors have been implicated as key factors in tumor angiogenesis that are up-regulated by hypoxia. We evaluated the effects of DNA-binding small molecules on hypoxia-inducible transcription of VEGF. A synthetic pyrrole-imidazole polyamide designed to bind the hypoxia response element (HRE) was found to disrupt hypoxia-inducible factor (HIF) binding to HRE. In cultured HeLa cells, this resulted in a reduction of VEGF mRNA and secreted protein l  ...[more]

Similar Datasets

Unknown MDM2 regulates vascular endothelial growth factor mRNA stabilization in hypoxia.
| S-EPMC3233029 | biostudies-literature
Unknown Monomeric gremlin is a novel vascular endothelial growth factor receptor-2 antagonist.
| S-EPMC5085234 | biostudies-literature
Unknown Inhibition of Hypoxia-Inducible Factor-1? and Vascular Endothelial Growth Factor by Chrysin in a Rat Model of Choroidal Neovascularization.
| S-EPMC7215732 | biostudies-literature
Unknown Overcoming evasive resistance from vascular endothelial growth factor a inhibition in sarcomas by genetic or pharmacologic targeting of hypoxia-inducible factor 1α.
| S-EPMC3677782 | biostudies-literature
Unknown Vascular Endothelial Cell-Specific Connective Tissue Growth Factor (CTGF) Is Necessary for Development of Chronic Hypoxia-Induced Pulmonary Hypertension.
| S-EPMC5835098 | biostudies-literature
Clinical PAVES: Pegfilgrastim Anti-vascular Endothelial Growth Factor (VEGF) Evaluation Study
| 2073020 | ecrin-mdr-crc
Unknown Vascular endothelial growth factor pathway.
| S-EPMC3086058 | biostudies-literature
Unknown Structure-Guided Molecular Engineering of a Vascular Endothelial Growth Factor Antagonist to Treat Retinal Diseases.
| S-EPMC7596137 | biostudies-literature
Unknown Expression of vascular endothelial growth factor, hypoxia inducible factor 1alpha, and carbonic anhydrase IX in human tumours.
| S-EPMC1770303 | biostudies-literature
Unknown Rnd3/RhoE Modulates Hypoxia-Inducible Factor 1?/Vascular Endothelial Growth Factor Signaling by Stabilizing Hypoxia-Inducible Factor 1? and Regulates Responsive Cardiac Angiogenesis.
| S-EPMC4752414 | biostudies-literature