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Genome-wide binding data for TRIM24 in androgen-dependent and castration-resistant prostate cancer cells

ABSTRACT: We report a novel and important role for the TRIM24-dependent transcriptional program in promoting prostate cancer progression to a castration-resistant state.

ORGANISM(S): Homo sapiens

PROVIDER: GSE69331 | GEO | 2016/05/27

SECONDARY ACCESSION(S): PRJNA285229

REPOSITORIES: GEO

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Identification of TRIM24-dependent gene expression programs in prostate cancer cells.

Project description:In this experiment we are exploring which genes are regulated by TRIM24 in androgen-dependent and castration-resistant prostate cancer cells.

2016-05-27 | GSE69330 | GEO

Androgen receptor gene aberrations in circulating cell-free DNA: biomarkers of therapeutic resistance and response in castration-resistant prostate cancer

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Persistent androgen receptor-mediated transcription in castration-resistant prostate cancer under androgen-deprived conditions

Project description:The androgen receptor (AR) is a ligand-inducible transcription factor that mediates androgen action in target tissues. Upon ligand binding, the AR binds to thousands of genomic loci and activates a cell-type specific gene program. Prostate cancer growth and progression depend on androgen-induced AR signalling. Treatment of advanced prostate cancer through medical or surgical castration leads to initial response and durable remission, but resistance inevitably develops. In castration-resistant prostate cancer (CRPC), AR activity remains critical for tumor growth despite androgen deprivation. While previous studies have focused on ligand-dependent AR signalling, in this study we explore AR function under the androgen-deprived conditions characteristic of CRPC. Our data demonstrate that the AR persistently occupies a distinct set of genomic loci after androgen deprivation in CRPC. These androgen-independent AR occupied regions have constitutively open chromatin structures that lack the canonical androgen response element and are independent of FoxA1, a transcription factor involved in ligand-dependent AR targeting. Many AR binding events occur at proximal promoters, which can act as enhancers to augment transcriptional activities of other promoters through DNA looping. We further show that androgen-independent AR binding directs a distinct gene expression program in CRPC, which is necessary for the growth of CRPC after androgen withdrawal. LNCaP, C4-2B, or 22RV1 cells were cultured in hormone-free media for 3 days and then treated with ethanol vehicle or DHT (10nM) for 4h or 16h prior to ChIP-seq or RNA-seq assays. For siRNA transfection, cells were transfected with AR siRNA or control siRNA for 3 days prior to RNA-seq assays.

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Persistent androgen receptor-mediated transcription in castration-resistant prostate cancer under androgen-deprived conditions

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The E3 ubiquitin ligase Siah2 contributes to castration-resistant prostate cancer by regulation of androgen receptor transcriptional activity cancer.

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The E3 ubiquitin ligase Siah2 contributes to castration-resistant prostate cancer by regulation of androgen receptor transcriptional activity cancer.

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