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.
journal_name
Proc Natl Acad Sci U S Aauthors
Yeh JR,Mohan R,Crews CMdoi
10.1073/pnas.97.23.12782keywords:
subject
Has Abstractpub_date
2000-11-07 00:00:00pages
12782-7issue
23eissn
0027-8424issn
1091-6490pii
97/23/12782journal_volume
97pub_type
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