N-Myc Drives Neuroendocrine Prostate Cancer Initiated from Human Prostate Epithelial Cells.
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.
Lee, JK; Phillips, JW; Smith, BA; Park, JW; Stoyanova, T; McCaffrey, EF; Baertsch, R; Sokolov, A; Meyerowitz, JG; Mathis, C; Cheng, D; Stuart, JM; Shokat, KM; Gustafson, WC; Huang, J; Witte, ON
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