Nucleic Acids Research Advance Access originally published online on April 10, 2007
Nucleic Acids Research 2007 35(8):2767-2776; doi:10.1093/nar/gkm198
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Nucleic Acids Research, 2007, Vol. 35, No. 8 2767-2776
© 2007 The Author(s)
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Molecular Biology |
A promoting role of androgen receptor in androgen-sensitive and -insensitive prostate cancer cells
1Department of Urology and 2Department of Genetics, Stanford University School of Medicine, Stanford, CA 94305-5328, USA
*To whom correspondence should be addressed. Tel: + 1-650-498-7523; Fax: + 1-650-723-4200; Email: zsun{at}stanford.edu
Received February 21, 2007. Revised March 19, 2007. Accepted March 21, 2007.
Although the vital role of the androgen receptor (AR) has been well demonstrated in primary prostate cancers, its role in the androgen-insensitive prostate cancers still remains unclear. Here, we used a small hairpin RNA approach to directly assess AR activity in prostate cancer cells. Reduction of AR expression in the two androgen-sensitive prostate cancer cell lines, LNCaP and LAPC4, significantly decreased AR-mediated transcription and cell growth. Intriguingly, in two androgen-insensitive prostate cell lines, LNCaP-C42B4 and CWR22Rv1, knockdown of AR expression showed a more pronounced effect on AR-induced transcription and cell growth than androgen depletion. Using cDNA microarrays, we also compared the transcriptional profiles induced by either androgen depletion or AR knockdown. Although a significant number of transcripts appear to be regulated by both androgen depletion and AR knockdown, we observed a subset of transcripts affected only by androgen depletion but not by AR knockdown, and vice versa. Finally, we demonstrated a direct role for AR in promoting tumor formation and growth in a xenograft model. Taken together, our results elucidate an important role for the AR in androgen-insensitive prostate cancer cells, and suggest that AR can be used as a therapeutic target for androgen-insensitive prostate cancers.
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