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Role of transcription factor Ets‐1 in the apoptosis of human vascular endothelial cells
Author(s) -
Teruyama Kazuhide,
Abe Mayumi,
Nakano Toru,
IwasakaYagi Chika,
Takahashi Shoki,
Yamada Shogo,
Sato Yasufumi
Publication year - 2001
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.1112
Subject(s) - apoptosis , angiogenesis , umbilical vein , transcription factor , microbiology and biotechnology , inhibitor of apoptosis domain , ets transcription factor family , biology , endogeny , gene , chemistry , cancer research , caspase , programmed cell death , biochemistry , in vitro
Transcription factor Ets‐1 is induced in endothelial cells (ECs) by angiogenic factors, and promotes angiogenesis by inducing angiogenesis‐related genes such as MMPs and integrin β3. Here, we examined the effect of Ets‐1 on apoptosis in ECs. Overexpression of Ets‐1 in human umbilical vein endothelial cells (HUVECs) induced apoptosis under the serum‐deprived condition. VEGF inhibited apoptosis and augmented the DNA binding of Ets‐1 in HUVECs. The inhibition of transcriptional activity of endogenous Ets‐1 by a dominant negative molecule intensified the anti‐apoptotic effect of VEGF. Caspase inhibitors blocked apoptosis of HUVECs induced by Ets‐1. DNA array analysis showed that Ets‐1 up‐regulated pro‐apoptotic genes such as Bid, cytochrome p450, caspase‐4, p27, and p21 more than 2 fold, and down‐regualted anti‐apoptotic genes such as DAD‐1, AXL, Cox‐2, IAP‐2, and MDM‐2 less than 0.5 fold in HUVECs. These results indicate that Ets‐1 itself is pro‐apoptotic to ECs by modulating the expression of apoptosis‐related genes. © 2001 Wiley‐Liss, Inc.