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.
|Number of pages||9|
|Journal||Biochimica et Biophysica Acta - Molecular Cell Research|
|Publication status||Published - 2008 Sept|
Bibliographical noteFunding 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).
- Alternative splicing
- Endothelial cell
- Interferon regulatory factor
- Vessel sprouting
ASJC Scopus subject areas
- Molecular Biology
- Cell Biology