English   español  
Please use this identifier to cite or link to this item: http://hdl.handle.net/10261/61442
logo share SHARE logo core CORE   Add this article to your Mendeley library MendeleyBASE

Visualizar otros formatos: MARC | Dublin Core | RDF | ORE | MODS | METS | DIDL
Exportar a otros formatos:

DC FieldValueLanguage
dc.contributor.authorSegrelles, Carmen-
dc.contributor.authorLara, M. Fernanda-
dc.contributor.authorRuiz Macías, Sergio-
dc.identifierdoi: 10.1038/sj.onc.1209155-
dc.identifierissn: 0950-9232-
dc.identifiere-issn: 1476-5594-
dc.identifier.citationOncogene 25: 1174-1185 (2006)-
dc.description.abstractThe PI3K/PTEN/Akt signaling pathway has emerged in recent years as a main player in human cancers, increasing proliferation and decreasing apoptosis of transformed cells, and thus becoming a potential target for therapeutic intervention. Our previous data have demonstrated that Akt-mediated signaling is of a key relevance in the mouse skin carcinogenesis system, one of the best-known models of experimental carcinogenesis. Here, we investigated the involvement of several pathways as mediators of Akt-induced increased proliferation and tumorigenesis in keratinocytes. Tumors produced by subcutaneous injection of Akt-transformed keratinocytes showed increased Foxo3a phosphorylation, but no major alterations in p21Cip1/WAF1, p27 Kip1 or mdm2 expression and/or localization. In contrast, we found increased expression and nuclear localization of ΔNp63, β-catenin and Lef1. Concomitantly, we also found increased expression of c-myc and CycD1, targets of the β-catenin/Tcf pathway. Such increase is associated with increased phosphorylation and stabilization of c-myc protein as well as increased translation of c-myc and CycD1 due to mTOR activation. Using immunohistochemistry approaches in samples of oral dysplasias and human head and neck squamous cell carcinomas, we confirmed that increased Akt activation significantly correlates with increased ΔNp63 and CycD expression, c-myc phosphorylation and nuclear accumulation of β-catenin. Collectively, these results demonstrate that Akt is able to transform keratinocytes by specific mechanisms involving transcriptional and post-transcriptional processes.-
dc.description.sponsorshipThis work was partially supported by Grant SAF2002-01037 from the CICYT, La Caixa Foundation and GR/SAL/0103/2004 from CAM. -
dc.publisherNature Publishing Group-
dc.titleMolecular determinants of Akt-induced keratinocyte transformation-
dc.description.versionPeer Reviewed-
Appears in Collections:(IBMCC) Artículos
Files in This Item:
File Description SizeFormat 
accesoRestringido.pdf15,38 kBAdobe PDFThumbnail
Show simple item record

Related articles:

WARNING: Items in Digital.CSIC are protected by copyright, with all rights reserved, unless otherwise indicated.