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


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

  • 27050099

Electronic International Standard Serial Number (EISSN)

  • 1878-3686

Digital Object Identifier (DOI)

  • 10.1016/j.ccell.2016.03.001


  • eng

Conference Location

  • United States