A promoting role of androgen receptor in androgen-sensitive and -insensitive prostate cancer cells.
A promoting role of androgen receptor in androgen-sensitive and -insensitive prostate cancer cells.
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DOI：
10.1093/nar/gkm198
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发表时间：
2007
影响因子：
14.9
通讯作者：
Sun Z
中科院分区：
文献类型：
--
作者：
Li TH;Zhao H;Peng Y;Beliakoff J;Brooks JD;Sun Z
尽管雄激素受体(AR)在原发性前列腺癌中的重要作用已得到很好的证实，但其在雄激素不敏感前列腺癌中的作用仍不清楚。在这里，我们使用了一种小发夹RNA方法来直接评估前列腺癌细胞中的AR活性。雄激素敏感的两种前列腺癌细胞系LNCaP和LAPC4中AR表达的降低显著降低了AR介导的转录和细胞生长。有趣的是，在两个雄激素不敏感的前列腺细胞系LNCaP-C42B4和CWR22Rv1中，AR表达下调对AR诱导的转录和细胞生长的影响比雄激素枯竭更明显。利用基因芯片，我们还比较了雄激素耗竭或AR基因敲除所诱导的转录图谱。虽然有相当数量的转录本似乎同时受雄激素枯竭和AR基因敲除的调节，但我们观察到只受雄激素枯竭而不受AR基因敲除影响的转录子集，反之亦然。最后，我们在异种移植模型中证明了AR在促进肿瘤形成和生长中的直接作用。综上所述，我们的结果阐明了AR在雄激素不敏感的前列腺癌细胞中的重要作用，并表明AR可以作为雄激素不敏感的前列腺癌的治疗靶点。
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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影响因子：
82.9
作者：
Chen, CD;Welsbie, DS;Sawyers, CL
通讯作者：
Sawyers, CL
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Cleutjens, KBJM;vanEekelen, CCEM;Trapman, J
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作者：
Craft, N;Shostak, Y;Sawyers, CL
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Sawyers, CL
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作者：
Dull, T;Zufferey, R;Naldini, L
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Naldini, L