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

PJ Kaplan‐Lefko, TM Chen, MM Ittmann… - The …, 2003 - Wiley Online Library
PJ Kaplan‐Lefko, TM Chen, MM Ittmann, RJ Barrios, GE Ayala, WJ Huss, LA Maddison…
The Prostate, 2003Wiley Online Library
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 …
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. Prostate 55: 219–237, 2003. © 2003 Wiley‐Liss, Inc.
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