title: Pathobiology of autochthonous prostate cancer in a pre-clinical transgenic mouse model.
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.
authors.affiliation: Department of Molecular and Cellular Biology, Houston, Texas 77030, USA.
authors.forename: Paula J
authors.initials: PJ
authors.lastname: Kaplan-Lefko
authors.forename: Tsuey-Ming
authors.initials: TM
authors.lastname: Chen
authors.forename: Michael M
authors.initials: MM
authors.lastname: Ittmann
authors.forename: Roberto J
authors.initials: RJ
authors.lastname: Barrios
authors.forename: Gustavo E
authors.initials: GE
authors.lastname: Ayala
authors.forename: Wendy J
authors.initials: WJ
authors.lastname: Huss
authors.forename: Lisette A
authors.initials: LA
authors.lastname: Maddison
authors.forename: Barbara A
authors.initials: BA
authors.lastname: Foster
authors.forename: Norman M
authors.initials: NM
authors.lastname: Greenberg
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism / Q000473:pathology*; D000818:Animals; D015820:Cadherins / Q000378:metabolism; D002454:Cell Differentiation; D004195:Disease Models, Animal; D018450:Disease Progression; D004354:Drug Screening Assays, Antitumor / Q000379:methods*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007633:Keratins / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000473:pathology*; D011944:Receptors, Androgen / Q000378:metabolism
chemical_list: D015820:Cadherins; D011944:Receptors, Androgen; D007633:Keratins