Journal of Biological Chemistry
Volume 276, Issue 50, 14 December 2001, Pages 47171-47177
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THIS ARTICLE HAS BEEN RETRACTED
Down-regulation of Integrin αvβ3 Expression and Integrin-mediated Signaling in Glioma Cells by Adenovirus-mediated Transfer of Antisense Urokinase-type Plasminogen Activator Receptor (uPAR) and Sense p16 Genes*

https://doi.org/10.1074/jbc.M104334200
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open access

Interaction between the extracellular matrix and integrin receptors on cell surfaces leads not only to cell adhesion but also to intracellular signaling events that affect cell migration, proliferation, and survival. The vitronectin receptor αvβ3 integrin is of key importance in glioma cell biology. The expression of urokinase-type plasminogen activator receptor (uPAR) was recently shown to co-regulate with the expression of αvβ3 integrin. Moreover, restoration of the p16 protein in glioma cells inhibits the αvβ3 integrin-mediated spreading of those cells on vitronectin. Thus we hypothesized that adenovirus-mediated down-regulation of uPAR and overexpression of p16 might down-regulate the expression of αvβ3 integrin and the integrin-mediated signaling in glioma cells, thereby defeating the malignant phenotype. In this study, we used replication-deficient adenovirus vectors that contain either a uPAR antisense expression cassette (Ad-uPAR) or wild-type p16 cDNA (Ad-p16) and a bicistronic adenovirus construct in which both the uPAR antisense and p16 sense expression cassettes (Ad-uPAR/p16) are inserted in the E1-deleted region of the vector. Infecting the malignant glioma cell line SNB19 with Ad-uPAR, Ad-p16, or Ad-uPAR/p16 in the presence of vitronectin resulted in decreased αvβ3 integrin expression and integrin-mediated biological effects, including adhesion, migration, proliferation, and survival Our results support the therapeutic potential of simultaneously targeting uPAR and p16 in the treatment of gliomas.

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Published, JBC Papers in Press, September 25, 2001, DOI 10.1074/jbc.M104334200

*

This work was supported by National Institutes of Health Grants CA75557 and CA76350 (to J. S. R).The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.