Interferon regulatory factor-1 (IRF-1) regulates VEGF-induced angiogenesis in HUVECs

Jeong Heon Lee, Taehoon Chun, Sang Yoon Park, Seung Bae Rho

Research output: Contribution to journalArticlepeer-review

23 Citations (Scopus)

Abstract

Interferon regulatory factor-1 (IRF-1) is a tumor suppressor and transcriptional modulator that can regulate gene expression involved in cell growth control, induction of apoptosis, and post-translation modification. In this study, we found that IRF-1 inhibits endothelial cell angiogenesis using human umbilical vein endothelial cell (HUVECs) culture system. In addition, IRF-1 directly inhibited the tube formation of endothelial cells on Matrigel and reduced the expression of p-Akt, and p-eNOS, which play a significant role in angiogenesis when stimulated by VEGF. We also demonstrate that C-terminal region including transactivation domain (TA) of IRF-1 functions as a signal for its angiostatic activity, and is spliced in human tumor tissues. These findings indicate that splicing variant involving exons 7 of IRF-1 could potentially modulate anti-angiogenic effect of IRF-1. In overall, this study provides the first evidence for anti-angiogenic role of IRF-1, which may have therapeutic values for cancer and angiogenesis-associated diseases.

Original languageEnglish
Pages (from-to)1654-1662
Number of pages9
JournalBiochimica et Biophysica Acta - Molecular Cell Research
Volume1783
Issue number9
DOIs
Publication statusPublished - 2008 Sept

Bibliographical note

Funding Information:
We thank Drs. S. A. Martinis (Department of Biochemistry, University of Illinois at Urbana-Champaign, USA), and Richard Yoo (University of Washington) for critically reading the manuscript. This work was supported by the National Cancer Center (NCC-0810410-1).

Keywords

  • Alternative splicing
  • Angiogenesis
  • CAM
  • Endothelial cell
  • Interferon regulatory factor
  • Vessel sprouting

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Fingerprint

Dive into the research topics of 'Interferon regulatory factor-1 (IRF-1) regulates VEGF-induced angiogenesis in HUVECs'. Together they form a unique fingerprint.

Cite this