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http://hdl.handle.net/10261/81595
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Campo DC | Valor | Lengua/Idioma |
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dc.contributor.author | Aguilera, Óscar | - |
dc.contributor.author | Peña, Cristina | - |
dc.contributor.author | García, José M. | - |
dc.contributor.author | Larriba, María Jesús | - |
dc.contributor.author | Ordóñez-Morán, Paloma | - |
dc.contributor.author | Navarro, Diego | - |
dc.contributor.author | Barbáchano, Antonio | - |
dc.contributor.author | Ballestar, Estéban | - |
dc.contributor.author | Fraga, Mario F. | - |
dc.contributor.author | Esteller, Manel | - |
dc.contributor.author | Gamallo, Carlos | - |
dc.contributor.author | Bonilla, Félix | - |
dc.contributor.author | González-Sancho, José Manuel | - |
dc.contributor.author | Muñoz Terol, Alberto | - |
dc.date.accessioned | 2013-09-06T10:58:15Z | - |
dc.date.available | 2013-09-06T10:58:15Z | - |
dc.date.issued | 2007 | - |
dc.identifier.citation | Carcinogenesis 28(9)): 1877-1884 (2007) | es_ES |
dc.identifier.issn | 0143-3334 | - |
dc.identifier.uri | http://hdl.handle.net/10261/81595 | - |
dc.description.abstract | The Wnt–β-catenin pathway is aberrantly activated in most colon cancers. DICKKOPF-1 (DKK-1) gene encodes an extracellular Wnt inhibitor that blocks the formation of signalling receptor complexes at the plasma membrane. We report that 1α,25-dihydroxyvitamin D3 [1,25(OH)2D3], the most active vitamin D metabolite, increases the level of DKK-1 RNA and protein in human SW480-ADH colon cancer cells. This effect is dose dependent, slow and depends on the presence of a transcription-competent nuclear vitamin D receptor (VDR). Accordingly, 1,25(OH)2D3 activates a 2300 bp fragment of the human DKK-1 gene promoter. Chromatin immunoprecipitation assays revealed that 1,25(OH)2D3 treatment induced a pattern of histone modifications which is compatible with transcriptionally active chromatin. DKK-1 is expressed at high level in colon cancer cell lines with a differentiated phenotype such as Caco-2 or HT-29. Exogenous expression of E-cadherin into SW480-ADH cells results in a strong adhesive phenotype and a 17-fold increase in DKK-1 RNA. In contrast, an E-cadherin blocking antibody inhibits 1,25(OH)2D3-induced differentiation of SW480-ADH cells and DKK-1 gene expression. Remarkably, in vivo treatment with the vitamin D analogue EB1089 induced DKK-1 protein expression in SW480-ADH cells xenografted in immunodeficient mice, and a correlation was observed in the expression of VDR and DKK-1 RNA in a series of 32 human colorectal tumours. These data indicate that 1,25(OH)2D3 activates the transcription of the DKK-1 gene, probably in an indirect way that is associated to the promotion of a differentiated phenotype. DKK-1 gene induction constitutes a novel mechanism of inhibition of Wnt signalling and antitumour action by 1,25(OH)2D3. | es_ES |
dc.description.sponsorship | This work was supported by Grants from Ministerio de Educación y Ciencia (SAF2004-01015), Ministerio de Sanidad y Consumo ISCIII-RETIC (RD06/0020/0009), Fundación de Investigación Médica Mutua Madrileña, Comunidad de Madrid (S-GEN-0266-2006) and the European Union (MRTN-CT- 2005-019496, NucSys). | es_ES |
dc.language.iso | eng | es_ES |
dc.publisher | Oxford University Press | es_ES |
dc.rights | closedAccess | es_ES |
dc.title | The Wnt antagonist DICKKOPF-1 gene is induced by 1alpha,25-dihydroxyvitamin D3 associated to the differentiation of human colon cancer cells | es_ES |
dc.type | artículo | es_ES |
dc.identifier.doi | 10.1093/carcin/bgm094 | - |
dc.description.peerreviewed | Peer reviewed | es_ES |
dc.relation.publisherversion | http://dx.doi.org/10.1093/carcin/bgm094 | es_ES |
dc.identifier.e-issn | 1460-2180 | - |
dc.type.coar | http://purl.org/coar/resource_type/c_6501 | es_ES |
item.openairetype | artículo | - |
item.grantfulltext | none | - |
item.cerifentitytype | Publications | - |
item.openairecristype | http://purl.org/coar/resource_type/c_18cf | - |
item.fulltext | No Fulltext | - |
item.languageiso639-1 | en | - |
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