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

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 p21(CIP/WAF), a cyclin-dependent kinase inhibitor, in endothelial cells but not in embryonic or adult fibroblasts. Moreover, primary endothelial cells isolated from p53(-/-) and p21(CIP/WAF-/-) mice are resistant to the cytostatic activity of TNP-470. We also demonstrate that p21(CIP/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 p21(CIP/WAF) expression and subsequent growth arrest.

authors

Yeh JR,Mohan R,Crews CM

doi

10.1073/pnas.97.23.12782

keywords:

subject

Has Abstract

pub_date

2000-11-07 00:00:00

pages

12782-7

issue

23

eissn

0027-8424

issn

1091-6490

pii

97/23/12782

journal_volume

97

pub_type

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