Abstract
Prostate tumour growth is almost always dependent upon the androgen receptor pathway and hence therapies aimed at blocking this signalling axis are useful tools in the management of this disease. Unfortunately such therapies invariably fail; and the tumour progresses to an “androgen-independent” stage. In such cases androgen receptor expression is almost always maintained and much evidence exists to suggest that it may still be driving growth. One mechanism by which the receptor is thought to remain active is mutation. This review summarises the present data on androgen receptor mutations in prostate cancer, and how such substitutions offer a growth advantage by affecting cofactor interactions or by reducing ligand specificity. Such alterations appear to have a subsequent effect upon gene expression suggesting that tumours may “behave” differently dependent upon the ligand promoting growth and if a mutation is present.
Keywords: Prostate Cancer, Androgen Receptor, tumour progresses, ligand, DNA Binding Domain
Current Genomics
Title: The Role of Androgen Receptor Mutations in Prostate Cancer Progression
Volume: 10 Issue: 1
Author(s): G. N. Brooke and C. L. Bevan
Affiliation:
Keywords: Prostate Cancer, Androgen Receptor, tumour progresses, ligand, DNA Binding Domain
Abstract: Prostate tumour growth is almost always dependent upon the androgen receptor pathway and hence therapies aimed at blocking this signalling axis are useful tools in the management of this disease. Unfortunately such therapies invariably fail; and the tumour progresses to an “androgen-independent” stage. In such cases androgen receptor expression is almost always maintained and much evidence exists to suggest that it may still be driving growth. One mechanism by which the receptor is thought to remain active is mutation. This review summarises the present data on androgen receptor mutations in prostate cancer, and how such substitutions offer a growth advantage by affecting cofactor interactions or by reducing ligand specificity. Such alterations appear to have a subsequent effect upon gene expression suggesting that tumours may “behave” differently dependent upon the ligand promoting growth and if a mutation is present.
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Cite this article as:
Brooke N. G. and Bevan L. C., The Role of Androgen Receptor Mutations in Prostate Cancer Progression, Current Genomics 2009; 10 (1) . https://dx.doi.org/10.2174/138920209787581307
DOI https://dx.doi.org/10.2174/138920209787581307 |
Print ISSN 1389-2029 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5488 |
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