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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 patient-derived explants representing normal breast or ER+ invasive breast cancer tissue treated with E2 or E2+DHT (10 nM each) for 24 hours."],"repository":["ENA"],"description_synonyms":["cell cycle modulation, Malignant Neoplasm, tumor suppressor, cell cycle arrest, Neoplasms, oestrogen receptor positive breast cancer, Benign Neoplasm, Receptors, RNA-seq., Androgens Receptors, Tumor, Malignant, Client, Stanolone Receptor, DHTR, 5 alpha Dihydrotestosterone Receptor, Androgen, positive regulation of cell cycle arrest, cell cycle regulator, Benign, arrest of mitotic cell cycle progression, estrogen-receptor positive breast cancer, modulation of cell cycle progression, Neoplasm, Androgens, Whole Transcriptome Shotgun Sequencing, 5, Androgen Receptors, 5 alpha-Dihydrotestosterone Receptor, Testosterone Receptor, ER+ breast cancer, average, Stanolone, alpha-Dihydrotestosterone Receptor, 5 alpha-Dihydrotestosterone, Malignancy, cell cycle control, Dihydrotestosterone, Benign Neoplasms, patient, Cancers, Stanolone Receptors, mitotic cell cycle arrest, Malignant Neoplasms, Neoplasias, control of cell cycle progression, Dihydrotestosterone Receptors, regulation of progression through cell cycle, Patient, regulation of cell cycle progression, Clients, regulation of cell cycle arrest, Testosterone, NR3C4, Androgen Receptor, Malignancies, Receptor, estrogen receptor positive breast cancer, other neoplasm, negative regulation of cell cycle arrest, cell cycle regulation, Neoplasia, Cancer, Tumors"],"name_synonyms":["cell cycle modulation, Malignant Neoplasm, tumor suppressor, cell cycle arrest, Neoplasms, oestrogen receptor positive breast cancer, Benign Neoplasm, Receptors, RNA-seq., Androgens Receptors, Tumor, Malignant, Client, Stanolone Receptor, DHTR, 5 alpha Dihydrotestosterone Receptor, Androgen, positive regulation of cell cycle arrest, cell cycle regulator, Benign, arrest of mitotic cell cycle progression, estrogen-receptor positive breast cancer, modulation of cell cycle progression, Neoplasm, Androgens, Whole Transcriptome Shotgun Sequencing, 5, Androgen Receptors, 5 alpha-Dihydrotestosterone Receptor, Testosterone Receptor, ER+ breast cancer, average, Stanolone, alpha-Dihydrotestosterone Receptor, 5 alpha-Dihydrotestosterone, Malignancy, cell cycle control, Dihydrotestosterone, Benign Neoplasms, patient, Cancers, Stanolone Receptors, mitotic cell cycle arrest, Malignant Neoplasms, Neoplasias, control of cell cycle progression, Dihydrotestosterone Receptors, regulation of progression through cell cycle, Patient, regulation of cell cycle progression, Clients, regulation of cell cycle arrest, Testosterone, NR3C4, Androgen Receptor, Malignancies, Receptor, estrogen receptor positive breast cancer, other neoplasm, negative regulation of cell cycle arrest, cell cycle regulation, Neoplasia, Cancer, Tumors"],"additional_accession":[]},"is_claimable":false,"name":"The Androgen Receptor is a Tumor Suppressor in Estrogen Receptor Positive Breast Cancer [Normal and tumor patient-derived explant RNA-seq]","description":"The Androgen Receptor is a Tumor Suppressor in Estrogen Receptor Positive Breast Cancer [Normal and tumor patient-derived explant RNA-seq]","dates":{"last_updated":"2025-09-24","first_public":"2021-01-19"},"accession":"PRJNA509777","cross_references":{"GEO":["GSE123762"],"taxon":["9606"],"PubMed":["33462444"]}}