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Modeling prostate cancer: a perspective on transgenic mouse models

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Abstract

Despite considerable success in treatment of early stage localized prostate cancer (PC), acute inadequacy of late stage PC treatment and its inherent heterogeneity poses a formidable challenge. Clearly, an improved understanding of PC genesis and progression along with the development of new targeted therapies are warranted. Animal models, especially, transgenic immunocompetent mouse models, have proven to be the best ally in this respect. A series of models have been developed by modulation of expression of genes implicated in cancer-genesis and progression; mainly, modulation of expression of oncogenes, steroid hormone receptors, growth factors and their receptors, cell cycle and apoptosis regulators, and tumor suppressor genes have been used. Such models have contributed significantly to our understanding of the molecular and pathological aspects of PC initiation and progression. In particular, the transgenic mouse models based on multiple genetic alterations can more accurately address the inherent complexity of PC, not only in revealing the mechanisms of tumorigenesis and progression but also for clinically relevant evaluation of new therapies. Further, with advances in conditional knockout technologies, otherwise embryonically lethal gene changes can be incorporated leading to the development of new generation transgenics, thus adding significantly to our existing knowledge base. Different models and their relevance to PC research are discussed.

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Acknowledgements

This work is supported by a grant from the Sydney Foundation of Medical Research and a project grant from NH&MRC (510238), Australia.

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Authors and Affiliations

  1. Oncology Research Centre, Prince of Wales Hospital, Barker St., Randwick, NSW, 2031, Australia

    Varinder Jeet, Pamela J. Russell & Aparajita Khatri

  2. Department of Medicine, Clinical Medical School, University of New South Wales, Sydney, NSW, 2052, Australia

    Varinder Jeet, Pamela J. Russell & Aparajita Khatri

  3. Australian Prostate Cancer Research Centre, Queensland, Queensland University of Technology, 60 Musk Ave, Kelvin Grove, QLD, 4059, Australia

    Pamela J. Russell

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  1. Varinder Jeet
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  2. Pamela J. Russell
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  3. Aparajita Khatri
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Correspondence to Aparajita Khatri.

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Postscript

Although we have tried our best to include major studies, we apologize to all those researchers whose work could not be incorporated into this review.

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Jeet, V., Russell, P.J. & Khatri, A. Modeling prostate cancer: a perspective on transgenic mouse models. Cancer Metastasis Rev 29, 123–142 (2010). https://doi.org/10.1007/s10555-010-9212-9

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