Pathobiology of autochthonous prostate cancer in a pre-clinical transgenic mouse model.
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.
Kaplan-Lefko
Paula J
PJ
Department of Molecular and Cellular Biology, Houston, Texas 77030, USA.
Chen
Tsuey-Ming
TM
Ittmann
Michael M
MM
Barrios
Roberto J
RJ
Ayala
Gustavo E
GE
Huss
Wendy J
WJ
Maddison
Lisette A
LA
Foster
Barbara A
BA
Greenberg
Norman M
NM
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
D015820:Cadherins; D011944:Receptors, Androgen; D007633:Keratins