Androgen receptor co-regulation in prostate cancer  

作　　者：Dhirodatta Senapati Sangeeta Kumari Hannelore V.Heemers 

机构地区：[1]Department of Cancer Biology,Cleveland Clinic,Cleveland,OH,USA [2]Department of Urology,Cleveland Clinic,Cleveland,OH,USA [3]Department of Hematology/Medical Oncology,Cleveland Clinic,Cleveland,OH,USA

出　　处：《Asian Journal of Urology》2020年第3期219-232,共14页亚洲泌尿外科杂志（英文）

基　　金：supported by DOD PCRP award W81XWH-16-1-0404(HVH);NIH NCI grant CA166440(HVH).

摘　　要：Prostate cancer(PCa)progression relies on androgen receptor(AR)action.Preventing AR’s ligand-activation is the frontline treatment for metastatic PCa.Androgen deprivation therapy(ADT)that inhibits AR ligand-binding initially induces remission but eventually fails,mainly because of adaptive PCa responses that restore AR action.The vast majority of castration-resistant PCa(CRPC)continues to rely on AR activity.Novel therapeutic strategies are being explored that involve targeting other critical AR domains such as those that mediate its constitutively active transactivation function,its DNA binding ability,or its interaction with co-operating transcriptional regulators.Considerable molecular and clinical variability has been found in AR’s interaction with its ligands,DNA binding motifs,and its associated coregulators and transcription factors.Here,we review evidence that each of these levels of AR regulation can individually and differentially impact transcription by AR.In addition,we examine emerging insights suggesting that each can also impact the other,and that all three may collaborate to induce gene-specific AR target gene expression,likely via AR allosteric effects.For the purpose of this review,we refer to the modulating influence of these differential and/or interdependent contributions of ligands,cognate DNA-binding motifs and critical regulatory protein interactions on AR’s transcriptional output,which may influence the efficiency of the novel PCa therapeutic approaches under consideration,as co-regulation of AR activity.

关 键 词：ANDROGEN COREGULATOR Gene transcription Hormonal therapy ALLOSTERY 

分 类 号：R737.25[医药卫生—肿瘤]