Novel oncogene-induced metastatic prostate cancer cell lines define human prostate cancer progression signatures

Cancer Res. 2013 Jan 15;73(2):978-89. doi: 10.1158/0008-5472.CAN-12-2133. Epub 2012 Nov 30.

Abstract

Herein, murine prostate cancer cell lines, generated via selective transduction with a single oncogene (c-Myc, Ha-Ras, and v-Src), showed oncogene-specific prostate cancer molecular signatures that were recapitulated in human prostate cancer and developed lung metastasis in immune-competent mice. Interrogation of two independent retrospective cohorts of patient samples using the oncogene signature showed an ability to distinguish tumor from normal prostate with a predictive value for prostate cancer of 98% to 99%. In a blinded study, the signature algorithm showed independent substratification of reduced recurrence-free survival by Kaplan-Meier analysis. The generation of new oncogene-specific prostate cancer cell lines that recapitulate human prostate cancer gene expression, which metastasize in immune-competent mice, are a valuable new resource for testing targeted therapy, whereas the molecular signatures identified herein provides further value over current gene signature markers of prediction and outcome.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line, Tumor*
  • Cell Transformation, Neoplastic
  • Disease Progression
  • Disease-Free Survival
  • Genes, myc
  • Genes, ras
  • Genes, src
  • Lung Neoplasms / secondary
  • Male
  • Mice
  • Mice, Transgenic
  • Neoplasm Metastasis*
  • Oncogenes*
  • Predictive Value of Tests
  • Prostatic Neoplasms / genetics*
  • Prostatic Neoplasms / immunology
  • Prostatic Neoplasms / pathology
  • Transcriptome