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Potent stimulation of the androgen receptor instigates a viral mimicry response in prostate cancer

ABSTRACT: Potent stimulation of the androgen receptor instigates a viral mimicry response in prostate cancer

PROVIDER: PRJNA777544 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR16761405_1.fastq.gz	Fastqsanger.gz
	SRR16761405_2.fastq.gz	Fastqsanger.gz
	SRR16761406_1.fastq.gz	Fastqsanger.gz
	SRR16761406_2.fastq.gz	Fastqsanger.gz
	SRR16761407_1.fastq.gz	Fastqsanger.gz

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Potent stimulation of the androgen receptor instigates a viral mimicry response in prostate cancer [ChIP-seq]

Project description:Potent stimulation of the androgen receptor instigates a viral mimicry response in prostate cancer [ChIP-seq]

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Potent stimulation of the androgen receptor instigates a viral mimicry response in prostate cancer [RNA-seq]

Project description:Potent stimulation of the androgen receptor instigates a viral mimicry response in prostate cancer [RNA-seq]

| PRJNA777549 | ENA

Potent stimulation of the androgen receptor instigates a viral mimicry response in prostate cancer [ChIP-seq]

Project description:Inhibiting the androgen receptor (AR), a ligand-activated transcription factor, with androgen deprivation therapy is a standard-of-care treatment for metastatic prostate cancer (PCa). Paradoxically, activation of AR can also inhibit the growth of PCa in some patients and experimental systems, but the mechanisms underlying this phenomenon are poorly understood. This study exploited a potent synthetic androgen, methyltestosterone (MeT), to investigate AR agonist-induced growth inhibition. MeT strongly inhibited growth of PCa cells expressing AR, but not AR-negative models. Genes and pathways regulated by MeT were highly analogous to those regulated by DHT, although MeT induced a quantitatively greater androgenic response in PCa cells. MeT potently down-regulated DNA methyltransferases, leading to global DNA hypomethylation. These epigenomic changes were associated with dysregulation of transposable element expression, with long-term MeT treatment resulting in upregulation of endogenous retrovirus (ERV) transcripts. Increased ERV expression led to accumulation of double-stranded RNA and a “viral mimicry” response characterised by activation of interferon signalling, upregulation of MHC Class I molecules and enhanced recognition of murine PCa cells by CD8+ T cells. Positive associations between AR activity and ERVs/anti-viral pathways were evident in patient transcriptomic data, supporting the clinical relevance of our findings. Collectively, our study reveals that the potent androgen MeT can increase the immunogenicity of PCa cells via a viral mimicry response, a finding that has potential implications for the development of strategies to sensitize this cancer type to immunotherapies.

2022-02-01 | GSE188150 | GEO

Potent stimulation of the androgen receptor instigates a viral mimicry response in prostate cancer [RNA-seq]

2022-02-01 | GSE187413 | GEO

Potent stimulation of the androgen receptor instigates a viral mimicry response in prostate cancer

Project description:This SuperSeries is composed of the SubSeries listed below.

2022-02-01 | GSE187414 | GEO

Epigenomic and transcriptomic profiles a of prostate cancer cell line with and without androgen stimulation

Project description:We performed H3K27ac ChIP-seq, ATAC-seq, and RNA-seq in LNCaP with and without androgen stimulation

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Androgen stimulation time-course of TMPRSS2-ERG fusion positive VCaP cells.

Project description:The TMPRSS2-ERG fusion positive prostate cancer cell line VCaP was grown for 72h in steroid depleted media (RPMI 10% CDT FBS) prior to vehicle (ethanol) or androgen stimulation (1nM R1881). To allow detailed analysis of androgen regulated gene expression in the VCaP prostate cancer cell line total RNA was harvested every every hour up to 24h using trizol (Sigma), quantified using a Nanodrop spectrophotometer (ND-1000). RNA samples were prepared for analysis on Illumina Human 12 v3 BeadArrays. Raw bead-summary data were generated using GenomeStudio version 1.9.0 (Illumina Inc.). For integrative analysis expression array data were normalised in R using the beadarray software and BASH (see Supplementary Methods for details) (Cairns et al., 2008; Dunning et al., 2007).

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Androgen receptor cistrome in breast cancer cell line MDA-MB-453 with 5a-dihydrotestosterone (DHT) stimulation

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