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

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • 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

Published Date

  • April 11, 2016

Published In

Volume / Issue

  • 29 / 4

Start / End Page

  • 536 - 547

PubMed ID

  • 27050099

Pubmed Central ID

  • PMC4829466

Electronic International Standard Serial Number (EISSN)

  • 1878-3686

Digital Object Identifier (DOI)

  • 10.1016/j.ccell.2016.03.001


  • eng

Conference Location

  • United States