Cross-Resistance to Abiraterone and Enzalutamide in Castration Resistance Prostate Cancer Cellular Models Is Mediated by AR Transcriptional Reactivation
| Autor: | Ignacio Puche-Sanz, Pedro J. Real, Pablo Lupiañez, Sonia Perales, Iris Simon, Clara Alaminos, José A. Lorente, Alba Rodríguez-Martínez, Laura Casado-Medina, Juan J. Díaz-Mochón, María José Serrano, María del Carmen Garrido-Navas |
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| Přispěvatelé: | [Simon,I, Perales,S, Casado-Medina,L, Lupiañez,P, Real,PJ] GENyO, Centre for Genomics and Oncological Research, Pfizer-University of Granada-Andalusian Regional Government, Gene Regulation, Stem Cells & Development Lab, PTS Granada, Granada, Spain. [Simon,I, Real,PJ] Faculty of Science, Department of Biochemistry and Molecular Biology I, University of Granada, Granada, Spain. [Rodríguez-Martínez,A, Garrido-Navas,MDC, Lorente,JA, Serrano,MJ] GENyO, Centre for Genomics and Oncological Research, Pfizer-University of Granada-Andalusian Regional Government, Liquid Biopsy and Cancer Interception Group, PTS Granada, Granada, Spain. [Rodríguez-Martínez,A, Lorente,JA] Faculty of Medicine, Legal Medicine and Toxicology Department, University of Granada, Laboratory of Genetic Identification, Spain. [Garrido-Navas,MDC] Universidad Internacional de la Rioja, Logroño, Spain. [Puche-Sanz,I] Department of Urology, Bio-Health Research Institute (Instituto de Investigación Biosanitaria ibs.GRANADA), Hospital Universitario Virgen de las Nieves, University of Granada, Granada, Spain. [Diaz-Mochon, JJ] GENyO, Centre for Genomics and Oncological Research, Pfizer-University of Granada-Andalusian Regional Government, Nanochembio Lab, PTS Granada, Granada, Spain. [Diaz-Mochon,JJ] Department of Pharmaceutical and Organic Chemistry, Faculty of Pharmacy, Campus de Cartuja, University of Granada, Granada, Spain. [Alaminos,C] Department of Urology, University Hospital of Jaen, Jaen, Spain. [Serrano,MJ] Comprehensive Oncology Division, Clinical University Hospital, Virgen de las Nieves-IBS, Granada, Spain. [Serrano,MJ] Department of Pathological Anatomy, Faculty of Medicine, University of Granada, Granada, Spain. [Real, PJ] Bio-Health Research Institute (Instituto de Investigación Biosanitaria ibs.GRANADA), Personalized Oncology Group, Granada, Spain, This study was supported by the Institute of Health Carlos III, Spain (PI17/00989) to M.J.S. and cofunded by the European Regional Development Fund 'A way to build Europe' and the Ramon y Cajal (RYC-2015-18382) to P.J.R., funded by the Ministry of Economy and Competitiveness. A.R.-M. was supported by the predoctoral-University Teacher Training Program from the Ministry of Education, Culture and Sport (FPU14/05461), I.S. was supported by the Young Researcher program from University of Granada (Joven Personal Investigador-Fondo Social Europeo, Universidad de Granada (2018-19)) and a donation from Rolucan Association (Rota Lucha contra el Cancer). |
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Cancer Research Phenomena and Processes::Genetic Phenomena::Phenotype [Medical Subject Headings] castration resistant prostate cancer Cell Andrógenos urologic and male genital diseases Diseases::Male Urogenital Diseases::Urogenital Neoplasms::Genital Neoplasms Male::Prostatic Neoplasms::Prostatic Neoplasms Castration-Resistant [Medical Subject Headings] Androgen deprivation therapy chemistry.chemical_compound Prostate cancer 0302 clinical medicine Castration Resistance Anatomy::Cells::Cells Cultured::Cell Line [Medical Subject Headings] androgen receptor abiraterone transcriptional regulation Abiraterone Analytical Diagnostic and Therapeutic Techniques and Equipment::Diagnosis::Diagnostic Techniques and Procedures::Clinical Laboratory Techniques::Cytological Techniques::Cytophotometry::Flow Cytometry [Medical Subject Headings] medicine.diagnostic_test Chemicals and Drugs::Amino Acids Peptides and Proteins::Proteins::Protein Isoforms [Medical Subject Headings] enzalutamide lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens Androgen receptor medicine.anatomical_structure Elementos reguladores de la transcripción Oncology Chemicals and Drugs::Hormones Hormone Substitutes and Hormone Antagonists::Hormone Antagonists::Androgen Antagonists [Medical Subject Headings] 030220 oncology & carcinogenesis Castration resistant prostate cancer cross-resistance Check Tags::Male [Medical Subject Headings] lcsh:RC254-282 Phenomena and Processes::Genetic Phenomena::Genetic Processes::Gene Expression Regulation::RNA Processing Post-Transcriptional::RNA Splicing::Alternative Splicing [Medical Subject Headings] Article Flow cytometry 03 medical and health sciences Transcriptional regulation Psychiatry and Psychology::Behavior and Behavior Mechanisms::Motivation::Goals [Medical Subject Headings] Acetato de abiraterona medicine Chemicals and Drugs::Chemical Actions and Uses::Pharmacologic Actions::Physiological Effects of Drugs::Hormones Hormone Substitutes and Hormone Antagonists::Hormones::Androgens [Medical Subject Headings] Enzalutamide Cross-resistance Phenomena and Processes::Cell Physiological Phenomena::Cell Physiological Processes::Cell Growth Processes::Cell Proliferation [Medical Subject Headings] Cell growth business.industry Analytical Diagnostic and Therapeutic Techniques and Equipment::Surgical Procedures Operative::Urogenital Surgical Procedures::Castration [Medical Subject Headings] Neoplasias de la próstata resistentes a la castración medicine.disease 030104 developmental biology chemistry Novel hormonal agents Cancer research Chemicals and Drugs::Amino Acids Peptides and Proteins::Proteins::Receptors Cytoplasmic and Nuclear::Receptors Steroid::Receptors Androgen [Medical Subject Headings] business AR-V7 AR-V9 |
| Zdroj: | Cancers Digibug: Repositorio Institucional de la Universidad de Granada Universidad de Granada (UGR) Digibug. Repositorio Institucional de la Universidad de Granada instname Cancers, Vol 13, Iss 1483, p 1483 (2021) Volume 13 Issue 6 |
| ISSN: | 2072-6694 |
| Popis: | 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. Instituto de Salud Carlos III PI17/00989 European Regional Development Fund "A way to build Europe" Ramon y Cajal - Ministry of Economy and Competitiveness RYC-2015-18382 Ministry of Education, Culture and Sport FPU14/05461 University of Granada |
| Databáze: | OpenAIRE |
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