The Role of Androgen Receptor Mutations in Prostate Cancer Progression

被引:134
作者
Brooke, G. N. [1 ]
Bevan, C. L. [1 ]
机构
[1] Univ London Imperial Coll Sci Technol & Med, Dept Oncol, Androgen Signalling Lab, London W12 0NN, England
基金
英国医学研究理事会;
关键词
LIGAND-BINDING DOMAIN; NUCLEAR RECEPTOR; CRYSTAL-STRUCTURE; DNA-BINDING; TRANSCRIPTION ACTIVATION; ESTROGEN-RECEPTOR; TRANSACTIVATION DOMAIN; REPEAT LENGTHS; HINGE REGION; WILD-TYPE;
D O I
10.2174/138920209787581307
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:18 / 25
页数:8
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