%0 Journal Article
%A Simon, Iris
%A Perales, Sonia
%A Casado-Medina, Laura
%A Rodríguez-Martínez, Alba
%A Garrido-Navas, Maria Del Carmen
%A Puche-Sanz, Ignacio
%A Diaz-Mochon, Juan J
%A Alaminos, Clara
%A Lupiañez, Pablo
%A Lorente, Jose A
%A Serrano, María J
%A Real, Pedro J
%T Cross-Resistance to Abiraterone and Enzalutamide in Castration Resistance Prostate Cancer Cellular Models Is Mediated by AR Transcriptional Reactivation.
%D 2021
%@ 2072-6694
%U https://hdl.handle.net/10668/28438
%X 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.
%K AR-V7
%K AR-V9
%K Novel hormonal agents
%K abiraterone
%K androgen receptor
%K castration resistant prostate cancer
%K cross-resistance
%K enzalutamide
%K transcriptional regulation
%~