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Molecular and Cellular Biology, August 2002, p. 5912-5922, Vol. 22, No. 16
0270-7306/02/$04.00+0     DOI: 10.1128/MCB.22.16.5912-5922.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

{alpha}5ß1 Integrin Activates an NF-{kappa}B-Dependent Program of Gene Expression Important for Angiogenesis and Inflammation

Sharon Klein,1 Antonin R. de Fougerolles,2 Pamela Blaikie,1 Leila Khan,1 Angela Pepe,1 Cynthia D. Green,3 Victor Koteliansky,2 and Filippo G. Giancotti1*

Cellular Biochemistry and Biophysics Program, Sloan-Kettering Institute, Memorial Sloan-Kettering Cancer Center, New York, New York 10021,1 Biogen, Inc., Cambridge, Massachusetts 02142,2 CuraGen Corporation, New Haven, Connecticut 065113

Received 8 January 2002/ Returned for modification 27 February 2002/ Accepted 16 May 2002

GeneCalling, a genome-wide method of mRNA profiling, reveals that endothelial cells adhering to fibronectin through the {alpha}5ß1 integrin, but not to laminin through the {alpha}2ß1 integrin, undergo a complex program of gene expression. Several of the genes identified are regulated by the NF-{kappa}B transcription factor, and many are implicated in the regulation of inflammation and angiogenesis. Adhesion of endothelial cells to fibronectin activates NF-{kappa}B through a signaling pathway requiring Ras, phosphatidylinositol 3-kinase, and Rho family proteins, whereas adhesion to laminin has a limited effect. Retroviral transfer of the superrepressor of NF-{kappa}B, I{kappa}B-2A, blocks basic fibroblast growth factor-induced angiogenesis in vivo. These results suggest that engagement of the {alpha}5ß1 integrin promotes an NF-{kappa}B-dependent program of gene expression that coordinately regulates angiogenesis and inflammation.

* Corresponding author. Mailing address: Cellular Biochemistry and Biophysics Program, Memorial Sloan-Kettering Cancer Center, Box 216, 1275 York Ave., New York, NY 10021. Phone: (212) 639-6998. Fax: (212) 794-6236. E-mail: F-Giancotti{at}ski.mskcc.org.

Molecular and Cellular Biology, August 2002, p. 5912-5922, Vol. 22, No. 16
0022-538X/02/$04.00+0     DOI: 10.1128/MCB.22.16.5912-5922.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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