NDLI: The antiangiogenic agent TNP-470 requires p53 and p21CIP/WAF for endothelial cell growth arrest

Content Provider	PubMed Central
Author	Yeh, Jing-ruey J. Mohan, Royce Crews, Craig M.
Copyright Year	2000
Abstract	Targeting the endothelial cell cycle as an antiangiogenic strategy has been difficult given the ubiquitous expression of critical cell cycle regulators. Here, we show that the antiangiogenic drug TNP-470 displays striking cell-type specificity insofar as it induces the expression of p21CIP/WAF, a cyclin-dependent kinase inhibitor, in endothelial cells but not in embryonic or adult fibroblasts. Moreover, primary endothelial cells isolated from p53−/− and p21CIP/WAF−/− mice are resistant to the cytostatic activity of TNP-470. We also demonstrate that p21CIP/WAF−/− mice are resistant to the antiangiogenic activity of TNP-470 in the basic fibroblast growth factor corneal micropocket angiogenesis assay. We conclude that TNP-470 induces p53 activation through a unique mechanism in endothelial cells leading to p21CIP/WAF expression and subsequent growth arrest.
Related Links	http://dx.doi.org/10.1073/pnas.97.23.12782
Ending Page	12787
Page Count	6
Starting Page	12782
File Format	PDF
ISSN	00278424
e-ISSN	10916490
Journal	Proceedings of the National Academy of Sciences of the United States of America
Issue Number	23
Volume Number	97
Language	English
Publisher	The National Academy of Sciences
Publisher Date	2000-11-07
Access Restriction	Open
Rights Holder	The National Academy of Sciences
Subject Keyword	General Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

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The antiangiogenic agent TNP-470 requires p53 and p21CIP/WAF for endothelial cell growth arrest