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The Androgen Receptor is a Tumor Suppressor in Estrogen Receptor Positive Breast Cancer [ZR-75-1 cell line SRC-3 ChIP-seq]

ABSTRACT: The Androgen Receptor is a Tumor Suppressor in Estrogen Receptor Positive Breast Cancer [ZR-75-1 cell line SRC-3 ChIP-seq]

PROVIDER: PRJNA657257 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR12454884.fastq.gz	Fastqsanger.gz
	SRR12454885.fastq.gz	Fastqsanger.gz
	SRR12454886.fastq.gz	Fastqsanger.gz
	SRR12454887.fastq.gz	Fastqsanger.gz
	SRR12454888.fastq.gz	Fastqsanger.gz

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The Androgen Receptor is a Tumor Suppressor in Estrogen Receptor Positive Breast Cancer [ZR-75-1 cell line SRC-3 ChIP-seq]

Project description: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.

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ZR-75-1 microarray expression data

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