Standard treatment for metastatic prostate cancer (CaP) prevents ligand-activation of androgen receptor (AR). Despite initial remission, CaP progresses while relying on AR. AR transcriptional output controls CaP behavior and is an alternative therapeutic target, but its molecular regulation is poorly understood. Here, we show that action of activated AR partitions into fractions that are controlled preferentially by different coregulators. In a 452-AR-target gene panel, each of 18 clinically relevant coregulators mediates androgen-responsiveness of 0-57% genes and acts as a coactivator or corepressor in a gene-specific manner. Selectivity in coregulator-dependent AR action is reflected in differential AR binding site composition and involvement with CaP biology and progression. Isolation of a novel transcriptional mechanism in which WDR77 unites the actions of AR and p53, the major genomic drivers of lethal CaP, to control cell cycle progression provides proof-of-principle for treatment via selective interference with AR action by exploiting AR dependence on coregulators.
Pubmed ID: 28826481 RIS Download
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View all literature mentionsCell line LNCaP is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsThis polyclonal targets β-actin
View all literature mentionsThis monoclonal targets PRK1
View all literature mentionsThis monoclonal targets TIF2
View all literature mentionsThis monoclonal targets Human, Mouse, Rat, Monkey
View all literature mentionsThis polyclonal targets PGAM5 antibody
View all literature mentionsThis polyclonal targets WDR77
View all literature mentionsThis monoclonal targets Raised against amino acids 299-315 of AR of human origin.
View all literature mentionsThis monoclonal targets IRF-1 (D5E4) XP Rabbit mAb
View all literature mentionsThis polyclonal targets Ki67 antibody - Proliferation Marker
View all literature mentionsCell line VCaP is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line LNCaP clone FGC is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line VCaP is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsThis monoclonal targets IRF-1 (D5E4) XP Rabbit mAb
View all literature mentionsThis polyclonal targets WDR77
View all literature mentionsThis monoclonal targets Raised against amino acids 299-315 of AR of human origin.
View all literature mentionsThis monoclonal targets PRK1
View all literature mentionsThis monoclonal targets Human, Mouse, Rat, Monkey
View all literature mentionsThis monoclonal targets TIF2
View all literature mentionsThis polyclonal targets β-actin
View all literature mentionsThis polyclonal targets Ki67 antibody - Proliferation Marker
View all literature mentionsThis polyclonal targets PGAM5 antibody
View all literature mentionsCell line LNCaP clone FGC is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentions