Androgen receptor down regulation by small interference RNA induces cell growth inhibition in androgen sensitive as well as in androgen independent prostate cancer cells
Androgen receptor down regulation by small interference RNA induces cell growth inhibition in androgen sensitive as well as in androgen independent prostate cancer cells
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DOI：
10.1016/j.jsbmb.2005.04.029
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发表时间：
2005-08-01
影响因子：
4.1
通讯作者：
Eder, IE
中科院分区：
文献类型：
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作者：
Hååg, P;Bektic, J;Eder, IE
我们研究了用小干扰RNA分子（siRNA_AR（start））下调雄激素受体（AR）对雄激素敏感性LNCaP和雄激素非依赖性LNCaPabl前列腺癌细胞的影响，后者代表前列腺癌中治疗抗性发展的体外模型。尽管与雄激素敏感性LNCaP细胞相比，LNCaPabl细胞表达增加的AR水平，但响应于siRNA_AR（开始）处理，该蛋白质显著下调。这种AR下调导致两种细胞系中显著的细胞生长抑制。相比之下，缺乏AR表达的DU-145前列腺癌细胞不受siRNA_AR（开始）抑制。由于AR下调，两种细胞系LNCaP和LNCaPabl在细胞周期调控基因的主要变化方面具有高度相似的基因表达谱。细胞周期抑制因子p21（Waf 1/Cip 1）和细胞周期蛋白D1被siRNA_AR（start）处理显著上调，考虑到细胞周期蛋白表达向细胞周期阻滞的转变。控制分子有中度影响细胞增殖和基因expressions.In总结，我们发现，AR抑制与siRNA诱导细胞生长迟缓，雄激素敏感性以及雄激素非依赖性前列腺癌细胞，因此可能代表一个有趣的方法来打击乳腺癌难治性前列腺癌。(c)2005爱思唯尔有限公司保留所有权利。
We investigated the effects of androgen receptor (AR) down regulation with a small interference RNA molecule (siRNA_AR(start)) on androgen sensitive LNCaP and androgen independent LNCaPabl prostate cancer cells, the latter representing an in vitro model for the development of therapy resistance in prostate cancer. Although LNCaPabl cells express increased levels of AR in comparison with androgen sensitive LNCaP cells, the protein was significantly down regulated in response to siRNA_AR(start) treatment. This AR down regulation resulted in a marked cell growth inhibition in both cell lines. By contrast, DU-145 prostate cancer cells, which lack AR expression, were not inhibited by the siRNA_AR(start). In consequence to AR down regulation, both cell lines, LNCaP and LNCaPabl, shared a highly similar gene expression profile in terms of major changes in cell cycle regulatory genes. The cell cycle inhibitor p21(Waf1/Cip1) as well as cyclin D1 were significantly up regulated by siRNA_AR(start) treatment, considering a switch in cyclin expression towards cell cycle retardation. Control molecules had moderate effects on cell proliferation and gene expression, respectively.In summary, we found that AR inhibition with siRNA induces cell growth retardation in androgen sensitive as well as in androgen independent prostate cancer cells and thus may represent an interesting approach to combat hormone-refractory prostate cancer. (c) 2005 Elsevier Ltd. All rights reserved.