Enzalutamide-induced Proteolytic Degradation of the Androgen Receptor in Prostate Cancer Cells Is Mediated Only to a Limited Extent by the Proteasome System
| العنوان: | Enzalutamide-induced Proteolytic Degradation of the Androgen Receptor in Prostate Cancer Cells Is Mediated Only to a Limited Extent by the Proteasome System |
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| المؤلفون: | Christian Thomas, Nadine Gelbrich, Alexander Mustea, Matthias B Stope, Maria A Oster, Holger H.H. Erb, Clemens Cammann |
| المصدر: | Anticancer Research. 41:3271-3279 |
| بيانات النشر: | Anticancer Research USA Inc., 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | 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 |
| الوصف: | 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. |
| تدمد: | 1791-7530 0250-7005 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::7b48415996b68a3c0039a525e3edf92c https://doi.org/10.21873/anticanres.15113 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....7b48415996b68a3c0039a525e3edf92c |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 17917530 02507005 |
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