Sustained expression of early growth response protein-1 blocks angiogenesis and tumor growth

Markus Lucerna, Jiri Pomyje, Diana Mechtcheriakova, Alexandra Kadl, Florian Gruber, Martin Bilban, Yuri Sobanov, Gernot Schabbauer, Johannes Breuss, Oswald Wagner, Markus Bischoff, Matthias Clauss, Bernd R. Binder, Erhard Hofer

Research output: Contribution to journalArticle

58 Scopus citations

Abstract

Transient induction of the transcription factor early growth response protein-1 (EGR-1) plays a pivotal role in the transcriptional response of endothelial cells to the angiogenic growth factors vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF), which are produced by most tumors and are involved in the angiogenic switch. We report here that sustained expression of EGR-1 by recombinant adenoviruses in endothelial cells, however, leads to the specific induction of potent feedback inhibitory mechanisms, including strong up-regulation of transcriptional repressors, negative cell cycle check point effectors, proteins with established antiangiogenic activity, and several proapoptotic genes. Sustained EGR-1 expression consistently leads to an antiangiogenic state characterized by an altered responsiveness to VEGF and bFGF and a striking inhibition of sprouting and tubule formation in vitro. Furthermore, EGR-1-expressing viruses potently inhibit cell invasion and vessel formation in the murine Matrigel model and repress tumor growth in a murine fibrosarcoma model. We propose that gene therapy involving sustained EGR-1 expression may constitute a novel therapeutic principle in the treatment of cancer due to the simultaneous induction of multiple pathways of antiangiogenesis, growth arrest, and apoptosis induction in proliferating cells leading to preferential inhibition of angiogenesis and tumor growth.

Original languageEnglish (US)
Pages (from-to)6708-6713
Number of pages6
JournalCancer Research
Volume66
Issue number13
DOIs
StatePublished - Jul 1 2006

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Lucerna, M., Pomyje, J., Mechtcheriakova, D., Kadl, A., Gruber, F., Bilban, M., Sobanov, Y., Schabbauer, G., Breuss, J., Wagner, O., Bischoff, M., Clauss, M., Binder, B. R., & Hofer, E. (2006). Sustained expression of early growth response protein-1 blocks angiogenesis and tumor growth. Cancer Research, 66(13), 6708-6713. https://doi.org/10.1158/0008-5472.CAN-05-2732