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2014-02

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Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/120991

The PDGFRβ-AKT pathway contributes to CDDP-acquired resistance in testicular germ cell tumors

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https://doi.org/10.1158/1078-0432.CCR-13-1131

Resum

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.

Matèries

Malalties del testicle, Tumors, Càncer, Resistència als medicaments, Medicaments antineoplàstics, Cisplatí

Matèries (anglès)

Testis diseases, Tumors, Cancer, Drug resistance, Antineoplastic agents, Cisplatin

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Articles publicats en revistes (Ciències Fisiològiques)
Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))
Articles publicats en revistes (Patologia i Terapèutica Experimental)

Citació

JULIACHS MILÀ, Mercè, MUÑOZ, C., MOUTINHO, Cátia, VIDAL-BEL, August, CONDOM I MUNDÓ, Enric, ESTELLER, Manel, GRAUPERA I GARCIA-MILÀ, Mariona, CASANOVAS I CASANOVAS, Oriol, GERMÀ LLUCH, José ramón, VILLANUEVA GARATACHEA, Alberto, VIÑALS CANALS, Francesc. The PDGFRβ-AKT pathway contributes to CDDP-acquired resistance in testicular germ cell tumors. _Clinical Cancer Research_. 2014. Vol. 20, núm. 3, pàgs. 658-667. [consulta: 23 de gener de 2026]. ISSN: 1078-0432. [Disponible a: https://hdl.handle.net/2445/120991]

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