DESCRIPTION:

This gene set is from supplemental figure 1 and describes genes that are classified as co-regulators acting with the androgen receptor (AR) and further classified as having differences in protein expression between prostate cancer and benign prostate. This set was manually curated by the authors.

LABEL:

androgen receptor coregulators misregulated in PCa

SCORE TYPE:

Binary

DATE ADDED:

2018-04-03

DATE UPDATED:

2024-04-25

SPECIES:

AUTHORS:

Liu S, Kumari S, Hu Q, Senapati D, Venkadakrishnan VB, Wang D, DePriest AD, Schlanger SE, Ben-Salem S, Valenzuela MM, Willard B, Mudambi S, Swetzig WM, Das GM, Shourideh M, Koochekpour S, Falzarano SM, Magi-Galluzzi C, Yadav N, Chen X, Lao C, Wang J, Billaud JN, Heemers HV

TITLE:

A comprehensive analysis of coregulator recruitment, androgen receptor function and gene expression in prostate cancer.

JOURNAL:

eLife Aug 2017, Vol 6, pp. None

ABSTRACT:

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: 28826481
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