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The placental gene PEG10 promotes progression of neuroendocrine prostate cancer

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

ORGANISM(S): Homo sapiens

PROVIDER: GSE59986 | GEO | 2015/01/05

SECONDARY ACCESSION(S): PRJNA257211

REPOSITORIES: GEO

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The placental gene PEG10 promotes progression of neuroendocrine prostate cancer

Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

2015-01-05 | E-GEOD-59986 | biostudies-arrayexpress

The placental gene PEG10 promotes progression of neuroendocrine prostate cancer [aCGH]

Project description:Neuroendocrine prostate cancer (NEPC) is proliferative, invasive, and untreatable. Its molecular pathogenesis remains poorly understood but appears to require TP53 and RB1 aberration. In this study we modeled the development of NEPC from conventional prostatic adenocarcinoma using a unique patient-derived xenograft and identified up-regulation of the placental gene PEG10. We found that the androgen receptor and the E2F/RB pathway dynamically regulate distinct post-transcriptional and post-translational isoforms of PEG10 at different stages of NEPC development. In vitro, PEG10 promoted cell cycle progression from G0/G1 in the context of TP53 loss, and regulated Snail expression via TGF-β signaling to promote invasion. Finally we show in vivo proof of principal using antisense oligonucleotide that PEG10 is a novel therapeutic target for NEPC. Six patient-derived xenograft tumors from the LTL331 xenograft lineage (PMID: 24356420; http://www.livingtumorcentre.com/) after differing lengths of time post-host castration. No replicates.

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The placental gene PEG10 promotes progression of neuroendocrine prostate cancer [Expression]

Project description:Neuroendocrine prostate cancer (NEPC) is proliferative, invasive, and untreatable. Its molecular pathogenesis remains poorly understood but appears to require TP53 and RB1 aberration. In this study we modeled the development of NEPC from conventional prostatic adenocarcinoma using a unique patient-derived xenograft and identified up-regulation of the placental gene PEG10. We found that the androgen receptor and the E2F/RB pathway dynamically regulate distinct post-transcriptional and post-translational isoforms of PEG10 at different stages of NEPC development. In vitro, PEG10 promoted cell cycle progression from G0/G1 in the context of TP53 loss, and regulated Snail expression via TGF-? signaling to promote invasion. Finally we show in vivo proof of principal using antisense oligonucleotide that PEG10 is a novel therapeutic target for NEPC. 14 patient-derived xenograft tumors from the LTL331 xenograft lineage (PMID: 24356420; http://www.livingtumorcentre.com/) after differing lengths of time post-host castration. Three replicates present for days 1-3 post-host castration.

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The placental gene PEG10 promotes progression of neuroendocrine prostate cancer

Project description:The placental gene PEG10 promotes progression of neuroendocrine prostate cancer

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Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

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