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Dissecting cell-type-specific roles of androgen receptor in prostate homeostasis and regeneration through lineage tracing

ABSTRACT: We used RNA-seq to compare the gene expression profiles of adult mouse prostate luminal cells and luminal cells that have the androgen receptor (AR) gene deleted. Our analyses show that AR-null luminal cells have altered expression levels of genes involved in cell-matrix adhesion, cytoskeleton regulation, and MAPK and TGF-beta signaling pathways. These results are consistent with our finding that AR-null luminal cells have abnormal cell morphology and loss of cell polarity.

ORGANISM(S): Mus musculus

PROVIDER: GSE76724 | GEO | 2017/01/17

SECONDARY ACCESSION(S): PRJNA308459

REPOSITORIES: GEO

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Dissecting cell-type-specific roles of androgen receptor in prostate homeostasis and regeneration through lineage tracing.

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The¬¬¬ androgen receptor interacts with GATA3 to transcriptionally regulate a luminal epithelial cell phenotype in breast cancer

Project description:Background: The androgen receptor (AR) is a tumor suppressor in estrogen receptor (ER) positive breast cancer, a role sustained in some ER negative breast cancers. Key factors dictating AR genomic activity in a breast context are largely unknown. Herein, we employed an unbiased chromatin immunoprecipitation-based proteomic technique to identify endogenous AR interacting co-regulatory proteins in ER positive and negative models of breast cancer to gain new insight into mechanisms of AR signaling in this disease. Results: The DNA-binding factor GATA3 is identified and validated as a novel AR interacting protein in breast cancer cells irrespective of ER status. AR activation by the natural ligand 5α-dihydrotestosterone (DHT) increases nuclear AR-GATA3 interactions, resulting in AR-dependent enrichment of GATA3 chromatin binding at a sub-set of genomic loci. Silencing GATA3 reduces but does not prevent AR DNA binding and transactivation of genes associated with AR/GATA3 co-occupied loci, indicating a co-regulatory role for GATA3 in AR signaling. DHT-induced AR/GATA3 binding coincides with upregulation of luminal differentiation genes, including EHF and KDM4B, established master regulators of a breast epithelial cell lineage. These findings are validated in a patient-derived xenograft model of breast cancer. Interaction between AR and GATA3 is also associated with AR-mediated growth inhibition in ER positive and ER negative breast cancer.

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