Please use this identifier to cite or link to this item:
http://hdl.handle.net/2445/120991
Full metadata record
DC Field | Value | Language |
---|---|---|
dc.contributor.author | Juliachs Milà, Mercè | - |
dc.contributor.author | Muñoz, C. | - |
dc.contributor.author | Moutinho, Cátia | - |
dc.contributor.author | Vidal-Bel, August | - |
dc.contributor.author | Condom i Mundó, Enric | - |
dc.contributor.author | Esteller, Manel | - |
dc.contributor.author | Graupera i Garcia-Milà, Mariona | - |
dc.contributor.author | Casanovas i Casanovas, Oriol | - |
dc.contributor.author | Germà Lluch, José Ramón | - |
dc.contributor.author | Villanueva Garatachea, Alberto | - |
dc.contributor.author | Viñals Canals, Francesc | - |
dc.date.accessioned | 2018-03-22T10:43:30Z | - |
dc.date.available | 2018-03-22T10:43:30Z | - |
dc.date.issued | 2014-02 | - |
dc.identifier.issn | 1078-0432 | - |
dc.identifier.uri | http://hdl.handle.net/2445/120991 | - |
dc.description.abstract | Purpose: we examined whether PI3K-AKT or extracellular signal-regulated kinase (ERK) signaling pathways could play a role in the development of cisplatin (CDDP) resistance in testicular germ cell tumor (TGT) cells. Experimental design: we compared AKT and ERK activation levels in CDDP-sensitive testicular tumor cells and in their corresponding CDDP-resistant-derived cells. We also analyzed these pathways in orthotopic testicular tumors and human patient samples. Results: our results indicated that there was overactivation of AKT in CDDP-resistant cells compared with sensitive cells, but no effect on activated ERK levels. We observed an increase in mRNA and protein levels for platelet-derived growth factor (PDGF) receptor β and PDGF-B ligand. These were responsible for AKT overactivation in CDDP-resistant cells. When PDGFRβ levels were decreased by short hairpin RNA (shRNA) treatment or its activation was blocked by pazopanib, CDDP-resistant cells behaved like sensitive cells. Moreover, CDDP-resistant cells were more sensitive to incubation with PDGFRβ inhibitors such as pazopanib or sunitinib than sensitive cells, a finding consistent with these cells being dependent on this signaling pathway. We also found overexpression of PDGFRβ and pAKT in CDDP-resistant choriocarcinoma orthotopic tumor versus their CDDP-sensitive counterparts. Finally, we found high PDGFRβ levels in human testicular tumors, and overexpression in CDDP-resistant testicular choriocarcinomas compared with the CDDP-sensitive and nontreated tumors. Conclusions: the PDGFRβ-AKT pathway plays a critical role in the development of CDDP resistance in testicular tumoral cells. | - |
dc.format.extent | 10 p. | - |
dc.format.mimetype | application/pdf | - |
dc.language.iso | eng | - |
dc.publisher | American Association for Cancer Research | - |
dc.relation.isformatof | Versió postprint del document publicat a: https://doi.org/10.1158/1078-0432.CCR-13-1131 | - |
dc.relation.ispartof | Clinical Cancer Research, 2014, vol. 20, num. 3, p. 658-667 | - |
dc.relation.uri | https://doi.org/10.1158/1078-0432.CCR-13-1131 | - |
dc.rights | (c) American Association for Cancer Research, 2014 | - |
dc.source | Articles publicats en revistes (Ciències Fisiològiques) | - |
dc.subject.classification | Malalties del testicle | - |
dc.subject.classification | Tumors | - |
dc.subject.classification | Càncer | - |
dc.subject.classification | Resistència als medicaments | - |
dc.subject.classification | Medicaments antineoplàstics | - |
dc.subject.classification | Cisplatí | - |
dc.subject.other | Testis diseases | - |
dc.subject.other | Tumors | - |
dc.subject.other | Cancer | - |
dc.subject.other | Drug resistance | - |
dc.subject.other | Antineoplastic agents | - |
dc.subject.other | Cisplatin | - |
dc.title | The PDGFRβ-AKT pathway contributes to CDDP-acquired resistance in testicular germ cell tumors | - |
dc.type | info:eu-repo/semantics/article | - |
dc.type | info:eu-repo/semantics/acceptedVersion | - |
dc.identifier.idgrec | 638378 | - |
dc.date.updated | 2018-03-22T10:43:31Z | - |
dc.rights.accessRights | info:eu-repo/semantics/openAccess | - |
dc.identifier.pmid | 24277456 | - |
dc.identifier.pmid | 26088228 | - |
Appears in Collections: | Articles publicats en revistes (Patologia i Terapèutica Experimental) Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL)) Articles publicats en revistes (Ciències Fisiològiques) |
Files in This Item:
File | Description | Size | Format | |
---|---|---|---|---|
638378.pdf | 8.35 MB | Adobe PDF | View/Open |
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.