Silencing the Peroxiredoxin III gene inhibits cell proliferation in breast cancer
Silencing the Peroxiredoxin III gene inhibits cell proliferation in breast cancer
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DOI：
10.3892/ijo_00000507
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发表时间：
2010-02-01
影响因子：
5.2
通讯作者：
Bay, Boon-Huat
中科院分区：
文献类型：
--
作者：
Chua, Pei-Jou;Lee, Eng-Hong;Bay, Boon-Huat
过氧化还蛋白III(Prx III)是线粒体中发现的一种抗氧化蛋白，在线粒体内稳态中起着重要的作用。PRX III的异常表达与多种肿瘤的发生有关。在这项研究中，我们评估了PRX III在乳腺癌组织中的表达，并阐明了它在细胞增殖中的作用，细胞增殖是癌症的一个标志。应用免疫组织化学方法对106例乳腺癌组织芯片进行PRX III抗体染色，并与增殖细胞核抗原(PC NA)免疫组化染色结果进行相关性分析。为验证Prx III在细胞增殖中的作用，采用实时定量RT-PCR、Western blotting和免疫荧光等方法在体外分析了Prx III在mRNA和蛋白水平的表达。通过siRNA介导的Prx III沉默MDA-MB-231乳腺癌细胞，观察其对细胞周期的影响。研究发现，患者组织芯片样本中Prx III的表达与增殖标记物--增殖细胞核抗原免疫染色呈正相关。乳腺癌细胞株MCF-7和MDA-MB-231均表达Prx III，瞬时导入siPrx III可抑制MDA-MB-231细胞的增殖，使细胞周期停滞。这些数据表明，PRX III在细胞周期调节中具有重要作用，并可能成为乳腺癌的潜在增殖标记物。
Peroxiredoxin III (Prx III), an antioxidant protein found in mitochondria, plays an essential role in mitochondrial homeostasis. Aberrant expression of Prx III has been implicated in the tumorigenesis of various cancers. In this study, we evaluated the expression of Prx III in breast cancer tissues and elucidated its role in cell proliferation, a hallmark of cancer. Breast tissue microarrays comprising 106 breast cancer sections were stained with Prx III antibody using immunohistochemisty and correlated with proliferating cell nuclear antigen (PCNA) immunostaining. To validate the role of Prx III in cell proliferation, expression of Prx III was analyzed at the mRNA and protein levels by real-time RT-PCR, Western blotting and immunofluorescence in vitro. siRNA mediated silencing of Prx III in MDA-MB-231 breast cancer cells was performed and the effect on the cell cycle was examined. Prx III expression in patient tissue microarray samples was found to be positively associated with PCNA immunostaining, a proliferative marker. Prx III was expressed in both MCF-7 and MDA-MB-231 breast cancer cell lines and transient transfection with siPrx III in MDA-MB-231 cells induced inhibition of cell proliferation and cell cycle arrest. The data suggests that Prx III has a significant role in cell cycle regulation and could be a potential proliferation marker in breast cancer.