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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Suppression of androgen receptor-mediated gene expression by a sequence-specific DNA-binding polyamide
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Suppression of androgen receptor-mediated gene expression by a sequence-specific DNA-binding polyamide

机译：序列特异性DNA结合聚酰胺抑制雄激素受体介导的基因表达

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摘要

Androgen receptor (AR) is essential for the growth and progression of prostate cancer in both hormone-sensitive and hormone-refractory disease. A DNA-binding polyamide that targets the consensus androgen response element binds the prostate-specific antigen (PSA) promoter androgen response element, inhibits androgen-induced expression of PSA and several other AR-regulated genes in cultured prostate cancer cells, and reduces AR occupancy at the PSA promoter and enhancer. Down-regulation of PSA by this polyamide was comparable to that produced by the synthetic antian-drogen bicalutamide (Casodex) at the same concentration. Genome-wide expression analysis reveals that a similar number of transcripts are affected by treatment with the polyamide and with bicalutamide. Direct inhibition of the AR-DNA interface by sequence-specific DNA binding small molecules could offer an alternative approach to antagonizing AR activity.
机译：在激素敏感性和激素难治性疾病中，雄激素受体（AR）对于前列腺癌的生长和进展至关重要。靶向共有雄激素反应元件的DNA结合聚酰胺与前列腺特异性抗原（PSA）启动子雄激素反应元件结合，抑制雄激素诱导的PSA和其他几个AR调控基因在培养的前列腺癌细胞中的表达，并减少AR占用在PSA启动子和增强子上。该聚酰胺对PSA的下调与在相同浓度下由合成的雄激素比卡鲁胺（Casodex）产生的下调相当。全基因组表达分析表明，用聚酰胺和比卡鲁胺处理会影响相似数量的转录本。序列特异性DNA结合小分子对AR-DNA界面的直接抑制可提供另一种拮抗AR活性的方法。

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