TY - JOUR
T1 - Interferon regulatory factor-1 (IRF-1) regulates VEGF-induced angiogenesis in HUVECs
AU - Lee, Jeong Heon
AU - Chun, Taehoon
AU - Park, Sang Yoon
AU - Rho, Seung Bae
N1 - 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).
PY - 2008/9
Y1 - 2008/9
N2 - 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.
AB - 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.
KW - Alternative splicing
KW - Angiogenesis
KW - CAM
KW - Endothelial cell
KW - Interferon regulatory factor
KW - Vessel sprouting
UR - http://www.scopus.com/inward/record.url?scp=49149119083&partnerID=8YFLogxK
U2 - 10.1016/j.bbamcr.2008.04.006
DO - 10.1016/j.bbamcr.2008.04.006
M3 - Article
C2 - 18472010
AN - SCOPUS:49149119083
SN - 0167-4889
VL - 1783
SP - 1654
EP - 1662
JO - Biochimica et Biophysica Acta - Molecular Cell Research
JF - Biochimica et Biophysica Acta - Molecular Cell Research
IS - 9
ER -