RapidCaP, a novel GEM model for metastatic prostate cancer analysis and therapy, reveals myc as a driver of Pten-mutant metastasis. Academic Article uri icon

Overview

abstract

  • Genetically engineered mouse (GEM) models are a pillar of functional cancer research. Here, we developed RapidCaP, a GEM modeling system that uses surgical injection for viral gene delivery to the prostate. We show that in Pten deficiency, loss of p53 suffices to trigger metastasis to distant sites at greater than 50% penetrance by four months, consistent with results from human prostate cancer genome analysis. Live bioluminescence tracking showed that endogenous primary and metastatic disease responds to castration before developing lethal castration resistance. To our surprise, the resulting lesions showed no activation of Akt but activation of the Myc oncogene. Using RapidCaP, we find that Myc drives local prostate metastasis and is critical for maintenance of metastasis, as shown by using the Brd4 inhibitor JQ1. Taken together, our data suggest that a "MYC-switch" away from AKT forms a critical and druggable event in PTEN-mutant prostate cancer metastasis and castration resistance.

publication date

  • January 20, 2014

Research

keywords

  • Neoplasm Metastasis
  • PTEN Phosphohydrolase
  • Prostatic Neoplasms
  • Proto-Oncogene Proteins c-myc
  • Retroviridae
  • Tumor Suppressor Protein p53

Identity

PubMed Central ID

  • PMC4084646

Scopus Document Identifier

  • 84895823244

Digital Object Identifier (DOI)

  • 10.1158/2159-8290.CD-13-0346

PubMed ID

  • 24444712

Additional Document Info

volume

  • 4

issue

  • 3