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dc.contributor.authorAznar, Salvador-
dc.contributor.authorValerón, Pilar F.-
dc.contributor.authorLacal, Juan Carlos-
dc.date.accessioned2010-05-21T11:19:49Z-
dc.date.available2010-05-21T11:19:49Z-
dc.date.issued2003-07-
dc.identifier.citationMolecular Biology of the Cell 14(7): 3041-3054 (2003)en_US
dc.identifier.issn1059-1524-
dc.identifier.urihttp://hdl.handle.net/10261/24593-
dc.description14 pages, 7 figures.en_US
dc.description.abstractRho GTPases are overexpressed in a variety of human tumors contributing to both tumor proliferation and metastasis. Recently, several studies demonstrate an essential role of transcriptional regulation in Rho GTPases-induced oncogenesis. Herein, we demonstrate that RhoA, Rac1, and Cdc42 promote the expression of cyclooxygenase-2 (COX-2) at the transcriptional level by a mechanism that is dependent on the transcription factor nuclear factor-{kappa}B (NF-{kappa}B), but not Stat3, a transcription factor required for RhoA-induced tumorigenesis. With respect to RhoA, this effect is dependent on ROCK, but not PKN. Treatment of RhoA-, Rac1-, and Cdc42-transformed epithelial cells with Sulindac and NS-398, two well-characterized nonsteroid antiinflammatory drugs (NSAIDs), results in growth inhibition as determined by cell proliferation assays. Accordingly, tumor growth of RhoA-expressing epithelial cells in syngeneic mice is strongly inhibited by NS-398 treatment. The effect of NSAIDs over RhoA-induced tumor growth is not exclusively dependent on COX-2 because DNA-binding of NF-{kappa}B is also abolished upon NSAIDs treatment, resulting in complete loss of COX-2 expression. Finally, treatment of RhoA-transformed cells with Bay11-7083, a specific NF-{kappa}B inhibitor, leads to inhibition of cell proliferation. We suggest that treatment of human tumors that overexpress Rho GTPases with NSAIDs and drugs that target NF-{kappa}B could constitute a valid antitumoral strategy.en_US
dc.description.sponsorshipThis work was supported by grants SAF2001-2042 and SAF2002- 2437 from Ministerio de Ciencia y Tecnología. S.A.B. is a fellow from Fondo de Investigación Sanitaria (Instituto deSalud Carlos III).en_US
dc.format.extent745020 bytes-
dc.format.mimetypeapplication/pdf-
dc.language.isoengen_US
dc.publisherAmerican Society for Cell Biologyen_US
dc.rightsopenAccessen_US
dc.titleROCK and nuclear factor-{kappa}B–dependent activation of cyclooxygenase-2 by Rho GTPases: effects on tumor growth and therapeutic consequencesen_US
dc.typeartículoen_US
dc.description.peerreviewedPeer revieweden_US
dc.relation.publisherversionhttp://www.molbiolcell.org/cgi/content/full/14/7/3041en_US
dc.type.coarhttp://purl.org/coar/resource_type/c_6501es_ES
item.openairetypeartículo-
item.cerifentitytypePublications-
item.languageiso639-1en-
item.grantfulltextopen-
item.openairecristypehttp://purl.org/coar/resource_type/c_18cf-
item.fulltextWith Fulltext-
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