Show simple item record

dc.contributor.authorIglesias Badiola, Maite 
dc.contributor.authorFrontelo, Pilar
dc.contributor.authorGamallo, Carlos
dc.contributor.authorQuintanilla, Miguel
dc.date.accessioned2012-08-09T03:05:28Z
dc.date.available2012-08-09T03:05:28Z
dc.date.issued2000-06-26
dc.identifier.urihttp://hdl.handle.net/10641/318
dc.description.abstractSmad4 functions as a transcription factor TGF-β signalling. We have investigated the role of Smad4 in the TGF-β1 cell responses of transformed PDV keratinocytes, wich contain a Ras oncogene, and of nontumorigenic MCA3D keratinocytes, by transfecting both cell lines with a dominant-negative Smad4 construct. Smad4 mediates TGF-β1-induced p21cip1 as growth factor. TGF-β1 activates Ras/Erk signalling activity in both cell lines. PD098059, as a specific inhibitor of MEK, disminishes TGF-β1-induced p21cip1 levels in PDV cells. PDV dominant-negative Smad4 cell transfectants, but not MCA3D transfectants, showed constitutive hyperactivation of the Ras/Erk signalling pathway, increased secretion of urokinase, higher motility properties, and a change to a fibroblastoid cell morphology associated in vivo with teh transition from a well differentiated to a pooly differentiated tumour phenotype. Infection of MCA3D control and dominant negative Smad4 cell transfectants with retroviruses carying a Ras oncogene led to enhaced p21cip1 and urokinase secreted levels, independently of TGF-β1 stimulation, that where reduced by PD098059. These results suggest that Smad4 acts inhibiting Ras-dependent Erk signalling activity in Ras-transformed Keratinocytes. Loss of Smad4 function in these cells results in hyperactivation of Erk signalling and progression to undifferentiated carcinomas.spa
dc.language.isoengspa
dc.publisherMacmillan Publishersspa
dc.relation.ispartofseriesOncogene;19spa
dc.rightsAttribution-NonCommercial-NoDerivs 3.0 Spain*
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/3.0/es/*
dc.subjectTGF-β1spa
dc.subjectSmad4spa
dc.subjectRasspa
dc.subjectErkspa
dc.subjectUrokinasespa
dc.subjectCarcinomaspa
dc.titleBlocakde of Smad4 in transformed keratinocytes containing a Ras oncogene leads to hyperactivation of the Ras-dependent Erk signalling pathway associated with progression to undifferentiated carcinomasspa
dc.typearticlespa


Files in this item

FilesSizeFormatView
blockade of smad.pdf9.922MbPDFView/Open

This item appears in the following Collection(s)

Show simple item record

Attribution-NonCommercial-NoDerivs 3.0 Spain
Except where otherwise noted, this item's license is described as Attribution-NonCommercial-NoDerivs 3.0 Spain