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Advances in mouse models of prostate cancer

Published online by Cambridge University Press:  09 June 2008

Imran Ahmad ,
Owen J. Sansom  and
Hing Y. Leung
Imran Ahmad*
Affiliation:
The Beatson Institute for Cancer Research, Glasgow, UK. Glasgow Citywide Urology, Greater Glasgow Health Board, Glasgow, UK.
Owen J. Sansom
Affiliation:
The Beatson Institute for Cancer Research, Glasgow, UK.
Hing Y. Leung
Affiliation:
The Beatson Institute for Cancer Research, Glasgow, UK. Glasgow Citywide Urology, Greater Glasgow Health Board, Glasgow, UK.
*
*Corresponding author: Imran Ahmad, The Beatson Institute for Cancer Research, Switchback Road, Bearsden, Glasgow, G61 1BD, UK. Tel: +44 141 330 3973; Fax: +44 141 942 6521; E-mail: imranahmad@doctors.net.uk
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Abstract

Advances in science and technology have allowed us to manipulate the mouse genome and analyse the effect of specific genetic alterations on the development of prostate cancer in vivo. We can now analyse the molecular basis of initiation, invasion and progression to metastatic disease. The current mouse models utilise knockout, knock-in or conditional regulation of expression using Cre–loxP technology. Genes that have been targeted include homeobox genes, tumour suppressors and oncogenes, growth factors (and their receptors), steroid hormones and cell-cycle regulators, as well as pro- and anti-apoptotic proteins. Bigenic models indicate that that two ‘hits’ are required for progression from intra-epithelial neoplasia (PIN) to invasion carcinoma, and two to five hits are needed for metastasis. Here, we discuss the numerous models that mimic various aspects of the disease process, such as PIN, locally invasive adenocarcinoma and metastatic disease. Currently the PB-Cre4 × PTENloxP/loxP mouse is the only model that spans the entire continuum from initiation to local invasion and metastasis. Such mouse models increase our understanding of the disease process and provide targets for novel therapeutic approaches. Hopefully, the transgenic models will become inducible and ultimately allow both temporal and spatial gene inactivation. Compound mutational models will also develop further, with double and triple knock-in or knockout systems adding to our knowledge of the interaction between different signalling cascades.

Type
Review Article
Information
Expert Reviews in Molecular Medicine , Volume 10 , October 2008 , e16
Copyright
Copyright © Cambridge University Press 2008

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References

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Further reading, resources and contacts

Mouse models of Human Cancer Consortium (MMHCC) Prostate Cancer Site. This website offers a brief introduction to prostate cancer, including cancer incidence, diagnosis, treatment and murine modelling of the disease:

http://emice-stage.nci.nih.gov/emice/mouse_models/organ_models/prostate_modelsGoogle Scholar
http://www.jax.org/about/index.htmlGoogle Scholar
http://emice-stage.nci.nih.gov/emice/mouse_models/organ_models/prostate_modelsGoogle Scholar
http://www.jax.org/about/index.htmlGoogle Scholar