
Biology Direct, Journal Year: 2024, Volume and Issue: 19(1)
Published: Nov. 11, 2024
Dysregulated androgen receptor (AR) activity is central to various diseases, particularly prostate cancer (PCa), in which it drives tumour initiation and progression. Consequently, antagonising AR via anti-androgens an indispensable treatment option for metastatic PCa. However, despite initial remission, drug resistance occurs. Therefore, the signalling pathway has been intensively investigated. role of protein stability therapy not yet deciphered. this study aimed investigate changes transactivity assess its mechanism as a possible target LNCaP, C4-2, 22Rv1 cells were treated with R1881, enzalutamide, cycloheximide, Rocaglamide. Mass spectrometry analyses performed on LNCaP identify pathways enriched by treatments. Western blotting was levels localisation changes. Changes determined qPCR. decipher molecular mechanisms underlying androgen- antiandrogen-induced alterations protein. Pathway analysis revealed enrichment proteins involved different that regulate translation. Translational proteasome inhibitor experiments these attributable modifications translational activity. Interestingly, effects castration-resistant PCa (CRPC) C4-2 or enzalutamide-resistant less prominent non-existent. This outcome similarly observed alteration transactivation, suppressed hormone-sensitive (HSPC) inhibition, akin effect enzalutamide. In contrast, treatment-resistant cell lines showed only slight change transcription. suggests HSPC, activation triggers cascade increases enhancing translation rate, thereby amplifying appears be dysregulated cells.
Language: Английский