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| Suppression of p53 activity and p21(WAF1/CIP1) expression by vascular cell integrin alpha v beta 3 during angiogenesis |
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| Author(s): Stromblad S, Becker JC, Yebra M, Brooks PC, Cheresh DA |
| Source: JOURNAL OF CLINICAL INVESTIGATION Volume: 98 Issue: 2 Pages: 426-433 Published: JUL 15 1996 |
| Times Cited: 293 References: 42 |
| Abstract: Induction of p53 activity in cells undergoing DNA synthesis represents a molecular conflict that can lead to apoptosis. During angiogenesis, proliferative endothelial cells become apoptotic in response to antagonists of integrin alpha v beta 3 and this leads to the regression of angiogenic blood vessels, thereby blocking the growth of various human tumors. Evidence is presented that administration of alpha v beta 3 antagonists during angiogenesis in vivo selectively caused activation of endothelial cell p53 and increased expression of the p53-inducible cell cycle inhibitor p21(WAF1/CIP1). In vitro studies revealed that the ligation state of human endothelial cell alpha v beta 3 directly influenced p53 activity and the bax cell death pathway. Specifically, agonists of endothelial cell alpha v beta 3, but not other integrins, suppressed p53 activity, blocked p21(WAF1/CIP1) expression, and increased the bcl-2/bax ratio, thereby promoting cell survival. Thus, ligation of vascular cell integrin alpha v beta 3 promotes a critical and specific adhesion-dependent cell survival signal during angiogenesis leading to inhibition of p53 activity, decreased expression of p21(WAF1/CIP1), and suppression of the bax cell death pathway. |
| Document Type: Article |
| Language: English |
Addresses:
1. Scripps Res Inst, DEPT IMMUNOL, LA JOLLA, CA 92037 USA
2. Scripps Res Inst, DEPT VASC BIOL, LA JOLLA, CA 92037 USA |
| Publisher: ROCKEFELLER UNIV PRESS, 222 E 70TH STREET, NEW YORK, NY 10021 |
| Subject Category: Medicine, Research & Experimental |
| IDS Number: VA160 |
| ISSN: 0021-9738 |
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| | | | | | | | | Record from Web of Science® | | | | | | | | | |