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Cross-Resistance to Abiraterone and Enzalutamide in Castration Resistance Prostate Cancer Cellular Models Is Mediated by AR Transcriptional Reactivation
dc.contributor.author | Simon, Iris | |
dc.contributor.author | Perales Romero, Sonia | |
dc.contributor.author | Casado Medina, Laura | |
dc.contributor.author | Rodríguez Martínez, Alba | |
dc.contributor.author | Garrido Navas, María del Carmen | |
dc.contributor.author | Puche Sanz, Ignacio | |
dc.contributor.author | Díaz Mochón, Juan José | |
dc.contributor.author | Lorente Acosta, José Antonio | |
dc.contributor.author | Lupiañez, Pablo | |
dc.contributor.author | Serrano, María José | |
dc.contributor.author | Real, Pedro J. | |
dc.date.accessioned | 2021-04-15T11:33:39Z | |
dc.date.available | 2021-04-15T11:33:39Z | |
dc.date.issued | 2021 | |
dc.identifier.citation | Simon, I.; Perales, S.; Casado-Medina, L.; Rodríguez-Martínez, A.; Garrido-Navas, M.d.C.; Puche-Sanz, I.; Diaz-Mochon, J.J.; Alaminos, C.; Lupiañez, P.; Lorente, J.A.; et al. Cross-Resistance to Abiraterone and Enzalutamide in Castration Resistance Prostate Cancer Cellular Models Is Mediated by AR Transcriptional Reactivation. Cancers 2021, 13, 1483. https://doi.org/ 10.3390/cancers13061483 | es_ES |
dc.identifier.uri | http://hdl.handle.net/10481/67961 | |
dc.description.abstract | Androgen deprivation therapy (ADT) and novel hormonal agents (NHAs) (Abiraterone and Enzalutamide) are the goal standard for metastatic prostate cancer (PCa) treatment. Although ADT is initially effective, a subsequent castration resistance status (CRPC) is commonly developed. The expression of androgen receptor (AR) alternative splicing isoforms (AR-V7 and AR-V9) has been associated to CRPC. However, resistance mechanisms to novel NHAs are not yet well understood. Androgen-dependent PCa cell lines were used to generate resistant models to ADT only or in combination with Abiraterone and/or Enzalutamide (concomitant models). Functional and genetic analyses were performed for each resistance model by real-time cell monitoring assays, flow cytometry and RT-qPCR. In androgen-dependent PCa cells, the administration of Abiraterone and/or Enzalutamide as first-line treatment involved a critical inhibition of AR activity associated with a significant cell growth inhibition. Genetic analyses on ADT-resistant PCa cell lines showed that the CRPC phenotype was accompanied by overexpression of AR full-length and AR target genes, but not necessarily AR-V7 and/or AR-V9 isoforms. These ADT resistant cell lines showed higher proliferation rates, migration and invasion abilities. Importantly, ADT resistance induced cross-resistance to Abiraterone and/or Enzalutamide. Similarly, concomitant models possessed an elevated expression of AR full-length and proliferation rates and acquired cross-resistance to its alternative NHA as second-line treatment. | es_ES |
dc.description.sponsorship | Instituto de Salud Carlos III PI17/00989 | es_ES |
dc.description.sponsorship | European Regional Development Fund "A way to build Europe" | es_ES |
dc.description.sponsorship | Ramon y Cajal - Ministry of Economy and Competitiveness RYC-2015-18382 | es_ES |
dc.description.sponsorship | Ministry of Education, Culture and Sport FPU14/05461 | es_ES |
dc.description.sponsorship | University of Granada | es_ES |
dc.language.iso | eng | es_ES |
dc.publisher | MDPI | es_ES |
dc.rights | Atribución 3.0 España | * |
dc.rights.uri | http://creativecommons.org/licenses/by/3.0/es/ | * |
dc.subject | Castration resistant prostate cancer | es_ES |
dc.subject | Androgen receptor | es_ES |
dc.subject | AR-V7 | es_ES |
dc.subject | AR-V9 | es_ES |
dc.subject | Transcriptional regulation | es_ES |
dc.subject | Novel hormonal agents | es_ES |
dc.subject | Abiraterone | es_ES |
dc.subject | Enzalutamide | es_ES |
dc.subject | Cross-resistance | es_ES |
dc.title | Cross-Resistance to Abiraterone and Enzalutamide in Castration Resistance Prostate Cancer Cellular Models Is Mediated by AR Transcriptional Reactivation | es_ES |
dc.type | journal article | es_ES |
dc.rights.accessRights | open access | es_ES |
dc.identifier.doi | 10.3390/cancers13061483 |