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The androgen receptor regulates a druggable translational regulon in advanced prostate cancer

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Mus musculus

PROVIDER: GSE116083 | GEO | 2019/07/31

REPOSITORIES: GEO

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The androgen receptor regulates a druggable translational regulon in advanced prostate cancer.

Project description: Not available

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The androgen receptor regulates a druggable translational regulon in advanced prostate cancer [ribosome profiling]

Project description:The recent advent of highly potent inhibitors of the androgen receptor and androgen biosynthesis has had the unfortunate iatrogenic effect of fueling new lethal prostate cancer phenotypes in patients. In particular, non-neuroendocrine androgen receptor-low castration resistant prostate cancer (AR low CRPC) is increasing in occurrence amongst patients and is uniformly fatal. The mechanisms that promote this phenotype remain poorly understood. Through molecular studies of murine and human models of AR low CRPC, we have identified a new functional interface between the androgen receptor and the translation initiation complex inhibitor 4EBP1. AR directly regulates 4EBP1 expression which translationally represses eIF4F complex formation and a pro-proliferation program. In the context of AR low prostate cancer, de-repression of translation initiation drives the aberrant expression of the pro-proliferation regulon which fuels uncontrolled cell growth. Genetic and pharmacologic inhibition of the downstream eIF4F translation initiation complex reverses the proliferation phenotype in vitro and in vivo. These findings reveal a new previously unrecognized druggable nexus which functionally link the processes of mRNA transcription and translation initiation in a rapidly emerging class of advanced lethal prostate cancer

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Project description:The androgen receptor regulates a druggable translational regulon in advanced prostate cancer [RNA-seq]

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Neuropilin-2 regulates androgen-receptor transcriptional activity in advanced prostate cancer

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

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Neuropilin-2 regulates androgen-receptor transcriptional activity in advanced prostate cancer [RNA-seq]

Project description:Gene expression was first compared between control and NRP2 depletd condition in prostate adenocarcinoma cell line LNCaP C4-2B . In the next set, we compared the gene expression between control and AR deplted state in LNCaP C4-2B cells.

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Neuropilin-2 regulates androgen-receptor transcriptional activity in advanced prostate cancer [ChIP-seq]

Project description:Our study using prostate cancer tissues and cell lines observed that neuropilin-2 (NRP2) can translocate to the nucleus of advanced prostate cancer cells. NRP2 is present in the nuclear membrane and near to the nuclear pore. To understand the functions of nuclear NRP2 in prostate cancer, we have performed NRP2-specific chromatin immunoprecipitation DNA-sequencing (ChIP-seq) in prostate cancer cell. Our results showed NRP2 forms a complex with transcription factors and pore proteins, which helps the transcription factors to be recruited at the promoter regions of genes. The nature of the interaction between NRP2-transcription factors is dynamic and depends on various physiological and pathological conditions. The ChIP-seq was carried in duplicate using adenocarcinoma cell lines.

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