Cooperative Dynamics of AR and ER Activity in Breast Cancer.

ABSTRACT: Androgen receptor (AR) is expressed in 90% of estrogen receptor alpha-positive (ER⁺) breast tumors, but its role in tumor growth and progression remains controversial. Use of two anti-androgens that inhibit AR nuclear localization, enzalutamide and MJC13, revealed that AR is required for maximum ER genomic binding. Here, a novel global examination of AR chromatin binding found that estradiol induced AR binding at unique sites compared with dihydrotestosterone (DHT). Estradiol-induced AR-binding sites were enriched for estrogen response elements and had significant overlap with ER-binding sites. Furthermore, AR inhibition reduced baseline and estradiol-mediated proliferation in multiple ER⁺/AR⁺ breast cancer cell lines, and synergized with tamoxifen and fulv

SUBMITTER: D'Amato NC 

PROVIDER: S-EPMC5107172 | biostudies-literature | 2016 Nov

REPOSITORIES: biostudies-literature