期刊
NUCLEIC ACIDS RESEARCH
卷 35, 期 8, 页码 2767-2776出版社
OXFORD UNIV PRESS
DOI: 10.1093/nar/gkm198
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资金
- Intramural NIH HHS [Z01 DK061002] Funding Source: Medline
- NCI NIH HHS [CA123532-01, R01 CA070297, R01 CA087767, R01 CA087767-05, K01 CA123532, R01 CA070297-12, CA70297, R29 CA070297, CA87767, R01 CA070297-11A2, R01 CA070297-10, R01 CA087767-04] Funding Source: Medline
- NIDDK NIH HHS [R01 DK061002, R01 DK061002-05, R01 DK061002-04, R56 DK061002] Funding Source: Medline
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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