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N-Myc Drives Neuroendocrine Prostate Cancer Initiated from Human Prostate Epithelial Cells.

ABSTRACT: MYCN amplification and overexpression are common in neuroendocrine prostate cancer (NEPC). However, the impact of aberrant N-Myc expression in prostate tumorigenesis and the cellular origin of NEPC have not been established. We define N-Myc and activated AKT1 as oncogenic components sufficient to transform human prostate epithelial cells to prostate adenocarcinoma and NEPC with phenotypic and molecular features of aggressive, late-stage human disease. We directly show that prostate adenocarcinoma and NEPC can arise from a common epithelial clone. Further, N-Myc is required for tumor maintenance, and destabilization of N-Myc through Aurora A kinase inhibition reduces tumor burden. Our findings establish N-Myc as a driver of NEPC and a target for therapeutic intervention.

SUBMITTER: Lee JK

PROVIDER: S-EPMC4829466 | biostudies-literature | 2016 Apr

REPOSITORIES: biostudies-literature

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N-Myc Drives Neuroendocrine Prostate Cancer Initiated from Human Prostate Epithelial Cells.

Lee John K JK Phillips John W JW Smith Bryan A BA Park Jung Wook JW Stoyanova Tanya T McCaffrey Erin F EF Baertsch Robert R Sokolov Artem A Meyerowitz Justin G JG Mathis Colleen C Cheng Donghui D Stuart Joshua M JM Shokat Kevan M KM Gustafson W Clay WC Huang Jiaoti J Witte Owen N ON

Cancer cell 20160331 4

MYCN amplification and overexpression are common in neuroendocrine prostate cancer (NEPC). However, the impact of aberrant N-Myc expression in prostate tumorigenesis and the cellular origin of NEPC have not been established. We define N-Myc and activated AKT1 as oncogenic components sufficient to transform human prostate epithelial cells to prostate adenocarcinoma and NEPC with phenotypic and molecular features of aggressive, late-stage human disease. We directly show that prostate adenocarcinom ...[more]

PMID: 27050099

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