Peroxiredoxin 2 in the nucleus and cytoplasm distinctly regulates androgen receptor activity in prostate cancer cells
Peroxiredoxin 2 in the nucleus and cytoplasm distinctly regulates androgen receptor activity in prostate cancer cells
复制标题
DOI：
10.1016/j.freeradbiomed.2011.04.001
复制
发表时间：
2011-07-01
影响因子：
7.4
通讯作者：
Naito, Seiji
中科院分区：
文献类型：
--
作者：
Shiota, Masaki;Yokomizo, Akira;Naito, Seiji
目前，很少有治疗方法对去势抵抗性前列腺癌有效。雄激素/雄激素受体（AR）信号通路的激活增加被认为可促进去势抵抗性前列腺癌。在此，我们报道过氧化物还蛋白（Prx）基因在去势抵抗前列腺癌和过氧化氢抵抗细胞中的表达上调。Prx2在去势抵抗性前列腺癌中mRNA和蛋白水平过表达，定位于细胞核和细胞质。Prx2的过表达增加了AR的转激活，而Prx2在细胞核中的过表达抑制了AR的转激活。通过在Cys（51）和Cys（172）中引入功能破坏突变，Prx2对AR活性的影响被消除了。沉默Prx2降低雄激素调节基因的表达，通过诱导细胞周期阻滞在Cl期抑制ar表达的前列腺癌细胞的生长。此外，Prx2敲低也抑制了去势抵抗前列腺癌细胞的细胞生长。这些发现表明Prx2通过调节AR活性参与表达AR的前列腺癌细胞的增殖。设计针对Prx2的治疗方法可能为开发前列腺癌（包括依赖于AR信号的去势抵抗性前列腺癌）的治疗方法提供一种新的策略。(C) 2011爱思唯尔公司版权所有。
Currently, few therapies are effective against castration-resistant prostate cancer. Increased activation of the androgen/androgen receptor (AR) signaling pathway is thought to promote castration-resistant prostate cancer. Herein, we report that peroxiredoxin (Prx) gene expression in castration-resistant prostate cancer and hydrogen peroxide-resistant cells was upregulated. Prx2 was overexpressed in castration-resistant prostate cancer at the mRNA and protein levels and was localized to the nucleus and cytoplasm. Overexpression of Prx2 increased AR transactivation, whereas Prx2 overexpression in the nucleus suppressed AR transactivation. These effects of Prx2 on AR activity were abolished by the introduction of function-disrupting mutations into Cys(51) and Cys(172). Silencing Prx2 reduced the expression of androgen-regulated genes and suppressed the growth of AR-expressing prostate cancer cells by inducing cell-cycle arrest at the Cl phase. Furthermore, Prx2 knockdown also suppressed cell growth in castration-resistant prostate cancer cells. These findings indicate that Prx2 is involved in the proliferation of AR-expressing prostate cancer cells by modulating AR activity. Designing therapeutics targeting Prx2 may offer a novel strategy for developing treatments for prostate cancer, including castration-resistant prostate cancer, which is dependent on AR signaling. (C) 2011 Elsevier Inc. All rights reserved.