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Title 

Hypoxia-responsive element-mediated soluble Tie2 vector exhibits an anti-angiogenic activity in vitro under hypoxic condition

Authors 

C H JeongY M LeeK S ChoiY R SeongY J KimDong Soo ImK W Kim

Publisher 

Spandidos Publications

Issue Date 

2005

Citation 

International Journal of Oncology, vol. 26, no. 1, pp. 211-216

Keywords 

hypoxia inducible factor 1hypoxia inducible factor 1alphahypoxia inducible factor 1betacell hypoxiaDNA responsive elementgene vectorgenetic vectorshypoxia-inducible factor

Abstract 

Hypoxia-inducible factor-1 (HIF-1) is one of the key mammalian transcription factors and shows increased levels in both protein stability and intrinsic transcriptional activity during low oxygen tension. Hypoxia-activated functional HIF-1 protein binds to hypoxia-responsive elements (HRE) in the enhancers of several genes including VEGF, the major player in angiogenesis, and initiates their mRNA expression. The molecular mechanisms regulating the gene expression under hypoxic conditions could increase the therapeutic window of tumor-specific delivery systems. In this study, to examine hypoxia-specific production of anti-angiogenic therapeutic gene, we constructed 5 copies of HRE (5xHRE) of human VEGF linked to soluble Tie2 (sTie2) driven by minimal SV40 promoter (5xHRE/SV40/sTie2). Our data showed that under hypoxia the secreted sTie2 selectively inhibited tube formation and migration capacities of endothelial cells in vitro. Hence, we propose that the vector system, 5xHRE/SV40/sTie2, might be a useful tool for down-regulating tumor angiogenesis under hypoxic condition.

ISSN 

1019-6439

Appears in Collections

1. Journal Articles > Journal Articles

Registered Date

2017-04-19


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