Enzalutamide-induced Proteolytic Degradation of the Androgen Receptor in Prostate Cancer Cells Is Mediated Only to a Limited Extent by the Proteasome System
| Autor: | Christian Thomas, Nadine Gelbrich, Alexander Mustea, Matthias B Stope, Maria A Oster, Holger H.H. Erb, Clemens Cammann |
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| Rok vydání: | 2021 |
| Předmět: |
Male
Proteasome Endopeptidase Complex Cancer Research Proteases Leupeptins Bortezomib chemistry.chemical_compound Ubiquitin Cell Line Tumor Antineoplastic Combined Chemotherapy Protocols Nitriles Phenylthiohydantoin MG132 medicine Humans Enzalutamide RNA Messenger Cell Proliferation biology Cell growth Prostate Prostatic Neoplasms General Medicine Androgen receptor Oncology chemistry Proteasome Drug Resistance Neoplasm Receptors Androgen Benzamides Proteolysis Cancer research biology.protein medicine.drug |
| Zdroj: | Anticancer Research. 41:3271-3279 |
| ISSN: | 1791-7530 0250-7005 |
| DOI: | 10.21873/anticanres.15113 |
| Popis: | Background/aim Androgen receptor (AR) degradation is the primary regulator of androgen receptor activity. This study was designed to investigate the influence of the proteasome on AR protein stability after enzalutamide (Enz) treatment. Materials and methods Cell counting after treatment was utilized to assess the effect of Enz on cell proliferation. Changes in mRNA levels were evaluated using reverse transcription-polymerase chain reaction (RT-PCR). Proteasome activity was assessed by measurement of the chymotrypsin-like activity of the beta-5 subunit of the proteasome. Changes in protein levels after treatment with Enz, MG132 (MG), bortezomib (Bor), or their combination were assessed using western blot analysis. Results Treatment with Enz led to a significant reduction of cell proliferation and AR protein levels. However, AR mRNA levels were unchanged. Inhibition of proteasome activity by MG counteracts the Enz-mediated AR degradation transiently, whereas Bor showed no inhibition of the Enz-mediated AR degradation. Conclusion Enz-mediated change in AR stability as an early and essential event after treatment was shown. However, investigations of the ubiquitin/proteasome system indicate involvement of several proteases in the Enz-mediated AR degradation process. |
| Databáze: | OpenAIRE |
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