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

Authors
  • Juhee Lee
  • Jw, Phillips
  • Ba, Smith
  • Jw, Park
  • T, Stoyanova
  • Ef, Mccaffrey
  • R, Baertsch
  • A, Sokolov
  • Jg, Meyerowitz
  • C, Mathis
  • D, Cheng
  • Josh Stuart
  • Km, Shokat
  • Wc, Gustafson
  • J, Huang
  • On, Witte
Type
Published Article
Journal
Cancer Cell
Publisher
Elsevier
Volume
29
Issue
4
Pages
536–547
Identifiers
DOI: 10.1016/j.ccell.2016.03.001
Source
UCSC Bioinformatics biomedical-ucsc
License
Unknown

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.

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