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dc.contributor.author | Aznar, Salvador | - |
dc.contributor.author | Valerón, Pilar F. | - |
dc.contributor.author | Lacal, Juan Carlos | - |
dc.date.accessioned | 2010-05-21T11:19:49Z | - |
dc.date.available | 2010-05-21T11:19:49Z | - |
dc.date.issued | 2003-07 | - |
dc.identifier.citation | Molecular Biology of the Cell 14(7): 3041-3054 (2003) | en_US |
dc.identifier.issn | 1059-1524 | - |
dc.identifier.uri | http://hdl.handle.net/10261/24593 | - |
dc.description | 14 pages, 7 figures. | en_US |
dc.description.abstract | Rho 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.sponsorship | This 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.extent | 745020 bytes | - |
dc.format.mimetype | application/pdf | - |
dc.language.iso | eng | en_US |
dc.publisher | American Society for Cell Biology | en_US |
dc.rights | openAccess | en_US |
dc.title | ROCK and nuclear factor-{kappa}B–dependent activation of cyclooxygenase-2 by Rho GTPases: effects on tumor growth and therapeutic consequences | en_US |
dc.type | artículo | en_US |
dc.description.peerreviewed | Peer reviewed | en_US |
dc.relation.publisherversion | http://www.molbiolcell.org/cgi/content/full/14/7/3041 | en_US |
dc.type.coar | http://purl.org/coar/resource_type/c_6501 | es_ES |
item.openairetype | artículo | - |
item.cerifentitytype | Publications | - |
item.languageiso639-1 | en | - |
item.grantfulltext | open | - |
item.openairecristype | http://purl.org/coar/resource_type/c_18cf | - |
item.fulltext | With Fulltext | - |
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