TY - JOUR T1 - Enzalutamide-induced Proteolytic Degradation of the Androgen Receptor in Prostate Cancer Cells Is Mediated Only to a Limited Extent by the Proteasome System JF - Anticancer Research JO - Anticancer Res SP - 3271 LP - 3279 DO - 10.21873/anticanres.15113 VL - 41 IS - 7 AU - HOLGER H. H. ERB AU - MARIA A. OSTER AU - NADINE GELBRICH AU - CLEMENS CAMMANN AU - CHRISTIAN THOMAS AU - ALEXANDER MUSTEA AU - MATTHIAS B. STOPE Y1 - 2021/07/01 UR - http://ar.iiarjournals.org/content/41/7/3271.abstract N2 - 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. ER -