SPOP Mutation Drives Prostate Tumorigenesis In Vivo through Coordinate Regulation of PI3K/mTOR and AR Signaling. Academic Article uri icon

Overview

abstract

  • Recurrent point mutations in SPOP define a distinct molecular subclass of prostate cancer. Here, we describe a mouse model showing that mutant SPOP drives prostate tumorigenesis in vivo. Conditional expression of mutant SPOP in the prostate dramatically altered phenotypes in the setting of Pten loss, with early neoplastic lesions (high-grade prostatic intraepithelial neoplasia) with striking nuclear atypia and invasive, poorly differentiated carcinoma. In mouse prostate organoids, mutant SPOP drove increased proliferation and a transcriptional signature consistent with human prostate cancer. Using these models and human prostate cancer samples, we show that SPOP mutation activates both PI3K/mTOR and androgen receptor signaling, effectively uncoupling the normal negative feedback between these two pathways.

publication date

  • March 13, 2017

Research

keywords

  • Mutation
  • Nuclear Proteins
  • Phosphatidylinositol 3-Kinases
  • Prostatic Neoplasms
  • Receptors, Androgen
  • Repressor Proteins
  • Signal Transduction
  • TOR Serine-Threonine Kinases

Identity

PubMed Central ID

  • PMC5384998

Scopus Document Identifier

  • 85015088542

Digital Object Identifier (DOI)

  • 10.1016/j.ccell.2017.02.004

PubMed ID

  • 28292441

Additional Document Info

volume

  • 31

issue

  • 3