Interferon regulatory factor-1 (IRF-1) regulates VEGF-induced angiogenesis in HUVECs.
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.
Lee
Jeong Heon
JH
Department of Obstetrics and Gynecology, Chonbuk National University Medical School, Jeonju 561-712, Republic of Korea.
Chun
Taehoon
T
Park
Sang-Yoon
SY
Rho
Seung Bae
SB
D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000818:Animals; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D002642:Chick Embryo; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism; D005091:Exons; D006801:Humans; D050856:Interferon Regulatory Factor-1 / Q000235:genetics / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009369:Neoplasms / Q000098:blood supply / Q000473:pathology; D009389:Neovascularization, Pathologic; D018919:Neovascularization, Physiologic / Q000187:drug effects; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors* / Q000378:metabolism; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism
D020533:Angiogenesis Inhibitors; D050856:Interferon Regulatory Factor-1; D000081082:Phosphoinositide-3 Kinase Inhibitors; D042461:Vascular Endothelial Growth Factor A; D040301:Vascular Endothelial Growth Factor Receptor-2; D051057:Proto-Oncogene Proteins c-akt