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

  • Authors:
    • Chul-Ho Jeong
    • You Mie Lee
    • Kyu-Sil Choi
    • Young Rim Seong
    • Yung-Jin Kim
    • Dong-Soo Im
    • Kyu-Won Kim
  • View Affiliations

  • Published online on: January 1, 2005     https://doi.org/10.3892/ijo.26.1.211
  • Pages: 211-216
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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.

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January 2005
Volume 26 Issue 1

Print ISSN: 1019-6439
Online ISSN:1791-2423

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APA
Jeong, C., Lee, Y.M., Choi, K., Seong, Y.R., Kim, Y., Im, D., & Kim, K. (2005). Hypoxia-responsive element-mediated soluble Tie2 vector exhibits an anti-angiogenic activity in vitro under hypoxic condition. International Journal of Oncology, 26, 211-216. https://doi.org/10.3892/ijo.26.1.211
MLA
Jeong, C., Lee, Y. M., Choi, K., Seong, Y. R., Kim, Y., Im, D., Kim, K."Hypoxia-responsive element-mediated soluble Tie2 vector exhibits an anti-angiogenic activity in vitro under hypoxic condition". International Journal of Oncology 26.1 (2005): 211-216.
Chicago
Jeong, C., Lee, Y. M., Choi, K., Seong, Y. R., Kim, Y., Im, D., Kim, K."Hypoxia-responsive element-mediated soluble Tie2 vector exhibits an anti-angiogenic activity in vitro under hypoxic condition". International Journal of Oncology 26, no. 1 (2005): 211-216. https://doi.org/10.3892/ijo.26.1.211