Pathobiology of autochthonous prostate cancer in a pre-clinical transgenic mouse model

Paula J. Kaplan-Lefko, Tsuey Ming Chen, Michael M. Ittmann, Roberto Barrios, Gustavo E. Ayala, Wendy J. Huss, Lisette A. Maddison, Barbara A. Foster, Norman M. Greenberg

Research output: Contribution to journalArticlepeer-review

350 Scopus citations

Abstract

BACKGROUND. Animal models that closely mimic clinical disease can be exploited to hasten the pace of translational research. To this end, we have defined windows of opportunity in the transgenic adenocarcinoma of the mouse prostate (TRAMP) model of prostate cancer as a paradigm for designing pre-clinical trials. METHODS. The incidence of cancer, metastasis, and distribution of pathology were examined as a function of time in TRAMP mice. The expression of various markers of differentiation were characterized. RESULTS. The TRAMP model develops progressive, multifocal, and heterogeneous disease. Each lobe of the prostate progressed at a different rate. Cytokeratin 8, E-cadherin, and androgen receptor (AR) were expressed during cancer progression but levels were reduced or absent in late stage disease. A distinct epithelial to neuroendocrine (ENT) shift was observed to be a stochastic event related to prostate cancer progression in TRAMP. CONCLUSIONS. This study will serve as the basis for the rational design of pre-clinical studies with genetically engineered mouse models.

Original languageEnglish (US)
Pages (from-to)219-237
Number of pages19
JournalProstate
Volume55
Issue number3
DOIs
StatePublished - May 15 2003

Keywords

  • Pathology
  • Pre-clinical trials
  • Prostate cancer
  • TRAMP

ASJC Scopus subject areas

  • Urology

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