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http://purl.uniprot.org/citations/15126605http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/15126605http://www.w3.org/2000/01/rdf-schema#comment"

Background

The basic region-leucine zipper protein c-Jun has been linked to cell proliferation, transformation, and apoptosis. However, a direct role for c-Jun in angiogenesis has not been shown.

Methods

We used human microvascular endothelial cells (HMEC-1) transfected with a DNAzyme targeting the c-Jun mRNA (Dz13), related oligonucleotides, or vehicle in in vitro models of microvascular endothelial cell proliferation, migration, chemoinvasion, and tubule formation, a rat model of corneal neovascularization, and a mouse model of solid tumor growth and vascular endothelial growth factor (VEGF)-induced angiogenesis. All statistical tests were two-sided.

Results

Compared with mock-transfected cells, HMEC-1 cells transfected with Dz13 expressed less c-Jun protein and possessed lower DNA-binding activity. Dz13 blocked endothelial cell proliferation, migration, chemoinvasion, and tubule formation. Dz13 inhibited the endothelial cell expression and proteolytic activity of MMP-2, a c-Jun-dependent gene. Dz13 inhibited VEGF-induced neovascularization in the rat cornea compared with vehicle control (Dz13 versus vehicle: 4.0 neovessels versus 30.7 neovessels, difference = 26.7 neovessels; P =.004; area occupied by new blood vessels for Dz13 versus vehicle: 0.35 mm2 versus 1.52 mm2, difference = 1.17 mm2; P =.005) as well as solid melanoma growth in mice (Dz13 versus vehicle at 14 days: 108 mm3 versus 283 mm3, difference = 175 mm3; P =.006) with greatly reduced vascular density (Dz13 versus vehicle: 30% versus 100%, difference = 70%; P<.001).

Conclusion

DNAzymes targeting c-Jun may have therapeutic potential as inhibitors of tumor angiogenesis and growth."xsd:string
http://purl.uniprot.org/citations/15126605http://purl.org/dc/terms/identifier"doi:10.1093/jnci/djh120"xsd:string
http://purl.uniprot.org/citations/15126605http://purl.uniprot.org/core/author"Zhang G."xsd:string
http://purl.uniprot.org/citations/15126605http://purl.uniprot.org/core/author"Khachigian L.M."xsd:string
http://purl.uniprot.org/citations/15126605http://purl.uniprot.org/core/author"Di Girolamo N."xsd:string
http://purl.uniprot.org/citations/15126605http://purl.uniprot.org/core/author"Sun L.Q."xsd:string
http://purl.uniprot.org/citations/15126605http://purl.uniprot.org/core/author"Dass C.R."xsd:string
http://purl.uniprot.org/citations/15126605http://purl.uniprot.org/core/author"Sumithran E."xsd:string
http://purl.uniprot.org/citations/15126605http://purl.uniprot.org/core/date"2004"xsd:gYear
http://purl.uniprot.org/citations/15126605http://purl.uniprot.org/core/name"J Natl Cancer Inst"xsd:string
http://purl.uniprot.org/citations/15126605http://purl.uniprot.org/core/pages"683-696"xsd:string
http://purl.uniprot.org/citations/15126605http://purl.uniprot.org/core/title"Effect of deoxyribozymes targeting c-Jun on solid tumor growth and angiogenesis in rodents."xsd:string
http://purl.uniprot.org/citations/15126605http://purl.uniprot.org/core/volume"96"xsd:string
http://purl.uniprot.org/citations/15126605http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/15126605
http://purl.uniprot.org/citations/15126605http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/15126605
http://purl.uniprot.org/uniprot/P17325#attribution-56CACBC6407FADB6A9C4CF5B8F6C0C8Ehttp://purl.uniprot.org/core/sourcehttp://purl.uniprot.org/citations/15126605
http://purl.uniprot.org/uniprot/#_P17325-mappedCitation-15126605http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/15126605
http://purl.uniprot.org/uniprot/P17325http://purl.uniprot.org/core/mappedCitationhttp://purl.uniprot.org/citations/15126605