|
Status |
Public on Jan 18, 2021 |
Title |
The Androgen Receptor is a Tumor Suppressor in Estrogen Receptor Positive Breast Cancer [ZR-75-1 xenograft RNA-seq] |
Organism |
Homo sapiens |
Experiment type |
Expression profiling by high throughput sequencing
|
Summary |
The role of the androgen receptor (AR) in estrogen receptor alpha (ER) positive breast cancer is controversial, constraining implementation of AR-directed therapies. Using a diverse, clinically relevant panel of cell-line and patient-derived models, we demonstrate that AR activation, not suppression, exerts potent anti-tumor activity in multiple disease contexts, including resistance to standard-of-care ER and CDK4/6 inhibitors. Importantly, AR agonists combined with standard-of-care agents enhanced therapeutic responses. Mechanistically, agonist activation of AR altered the genomic distribution of ER and essential co-activators (p300, SRC-3), resulting in repression of ER-regulated cell cycle genes and up-regulation of AR target genes, including known tumor suppressors. A gene signature of AR activity positively predicted disease survival in multiple clinical ER+ breast cancer cohorts. These findings provide unambiguous evidence that AR has a tumor suppressor role in ER+ breast cancer and support AR agonism as the optimal AR-directed treatment strategy, revealing a rational therapeutic opportunity.
|
|
|
Overall design |
RNA-seq of ZR-75-1 xenograft tumors treated for 5 days with either Vehicle, DHT, Enobosarm, or Enzalutamide.
|
|
|
Contributor(s) |
Hickey TE, Selth LA, Milioli HH, Roden D, Hui M, Swarbrick A, Lim W, Tilley WD |
Citation(s) |
33462444 |
Submission date |
Dec 13, 2018 |
Last update date |
Jan 26, 2021 |
Contact name |
Luke Selth |
E-mail(s) |
luke.selth@flinders.edu.au
|
Organization name |
Flinders University
|
Department |
College of Medicine and Public Health
|
Street address |
Flinders Drive
|
City |
Bedford Park |
State/province |
SA |
ZIP/Postal code |
5042 |
Country |
Australia |
|
|
Platforms (1) |
GPL16791 |
Illumina HiSeq 2500 (Homo sapiens) |
|
Samples (17)
|
|
This SubSeries is part of SuperSeries: |
GSE123770 |
The Androgen Receptor is a Tumor Suppressor in Estrogen Receptor Positive Breast Cancer |
|
Relations |
BioProject |
PRJNA509780 |
SRA |
SRP173369 |