Transcription of Nrdp1 by the androgen receptor is regulated by nuclear filamin A in prostate cancer

Endocrine-related Cancer
Rosalinda M SavoyParamita M Ghosh

Abstract

Prostate cancer (PCa) progression is regulated by the androgen receptor (AR); however, patients undergoing androgen-deprivation therapy (ADT) for disseminated PCa eventually develop castration-resistant PCa (CRPC). Results of previous studies indicated that AR, a transcription factor, occupies distinct genomic loci in CRPC compared with hormone-naïve PCa; however, the cause of this distinction was unknown. The E3 ubiquitin ligase Nrdp1 is a model AR target modulated by androgens in hormone-naïve PCa but not in CRPC. Using Nrdp1, we investigated how AR switches transcription programs during CRPC progression. The proximal Nrdp1 promoter contains an androgen response element (ARE); we demonstrated AR binding to this ARE in androgen-sensitive PCa. Analysis of hormone-naive human prostatectomy specimens revealed correlation between Nrdp1 and AR expression, supporting AR regulation of NRDP1 levels in androgen-sensitive tissue. However, despite sustained AR levels, AR binding to the Nrdp1 promoter and Nrdp1 expression were suppressed in CRPC. Elucidation of the suppression mechanism demonstrated correlation of NRDP1 levels with nuclear localization of the scaffolding protein filamin A (FLNA) which, as we previously showed, is itself r...Continue Reading

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Citations

Sep 9, 2016·Endocrine-related Cancer·Paramita M Ghosh
Feb 13, 2018·Cellular and Molecular Life Sciences : CMLS·Stefano Sala, Christophe Ampe
Jul 4, 2019·International Braz J Urol : Official Journal of the Brazilian Society of Urology·Xue-Chao LiLi-Jun Chen
Feb 13, 2018·Oncology Letters·Xinyi Yang, Ying Lin
Nov 23, 2016·Journal of Molecular Endocrinology·Alessandra MingioneSabrina Corbetta
Dec 18, 2020·Frontiers in Cell and Developmental Biology·Isabelle LamsoulPierre G Lutz
Mar 22, 2018·Journal of Proteome Research·Delphine MasschaeleJan Tavernier

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