Please use this identifier to cite or link to this item: https://hdl.handle.net/2440/17440
Citations
Scopus Web of Science® Altmetric
?
?
Type: Journal article
Title: Mutation of the androgen receptor causes oncogenic transformation of the prostate
Author: Han, G.
Buchanan, G.
Ittmann, M.
Harris, J.
Yu, X.
DeMayo, F.
Tilley, W.
Greenberg, N.
Citation: Proceedings of the National Academy of Sciences of USA, 2005; 102(4):1151-1156
Publisher: Natl Acad Sciences
Issue Date: 2005
ISSN: 0027-8424
1091-6490
Statement of
Responsibility: 
Guangzhou Han, Grant Buchanan, Michael Ittmann, Jonathan M. Harris, Xiaoqing Yu, Francesco J. DeMayo, Wayne Tilley and Norman M. Greenberg
Abstract: Recent evidence demonstrates that the androgen receptor (AR) continues to influence prostate cancer growth despite medical therapies that reduce circulating androgen ligands to castrate levels and/or block ligand binding. Whereas the mutation, amplification, overexpression of AR, or cross-talk between AR and other growth factor pathways may explain the failure of androgen ablation therapies in some cases, there is little evidence supporting a causal role between AR and prostate cancer. In this study, we functionally and directly address the role whereby AR contributes to spontaneous cancer progression by generating transgenic mice expressing (i) AR-WT to recapitulate increased AR levels and ligand sensitivity, (ii) AR-T857A to represent a promiscuous AR ligand response, and (iii) AR-E231G to model altered AR function. Whereas transgenes encoding either AR-WT or AR-T857A did not cause prostate cancer when expressed at equivalent levels, expression of AR-E231G, which carries a mutation in the most highly conserved signature motif of the NH2-terminal domain that also influences interactions with cellular coregulators, caused rapid development of prostatic intraepithelial neoplasia that progressed to invasive and metastatic disease in 100% of mice examined. Taken together, our data now demonstrate the oncogenic potential of steroid receptors and implicate altered AR function and receptor coregulator interaction as critical determinants of prostate cancer initiation, invasion, and metastasis.
Keywords: Animals
Mice, Transgenic
Mice
Prostatic Neoplasms
Cell Transformation, Neoplastic
Receptors, Androgen
Signal Transduction
Binding Sites
Amino Acid Sequence
Mutation
Molecular Sequence Data
Male
Rights: © 2005 by The National Academy of Sciences of the USA
DOI: 10.1073/pnas.0408925102
Published version: http://dx.doi.org/10.1073/pnas.0408925102
Appears in Collections:Aurora harvest 2
Medicine publications

Files in This Item:
There are no files associated with this item.


Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.