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沉默过氧化物酶 III 基因抑制乳腺癌细胞增殖。

Silencing the Peroxiredoxin III gene inhibits cell proliferation in breast cancer.

机构信息

Department of Anatomy, Yong Loo Lin School of Medicine, National University of Singapore, and Department of Pathology, Singapore General Hospital, MD10, S 117 597, Singapore.

出版信息

Int J Oncol. 2010 Feb;36(2):359-64.

PMID:20043069
Abstract

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.

摘要

过氧化物酶 III(Prx III)是一种存在于线粒体中的抗氧化蛋白,在维持线粒体稳态方面发挥着重要作用。Prx III 的异常表达与多种癌症的肿瘤发生有关。在这项研究中,我们评估了 Prx III 在乳腺癌组织中的表达,并阐明了其在细胞增殖(癌症的一个标志)中的作用。使用免疫组织化学法对包含 106 个乳腺癌切片的乳腺组织微阵列用 Prx III 抗体进行染色,并与增殖细胞核抗原(PCNA)免疫染色相关联。为了验证 Prx III 在细胞增殖中的作用,我们通过实时 RT-PCR、Western blot 和免疫荧光在体外分析了 Prx III 的表达。在 MDA-MB-231 乳腺癌细胞中通过 siRNA 介导的 Prx III 沉默,并检测对细胞周期的影响。在患者组织微阵列样本中发现 Prx III 的表达与 PCNA 免疫染色呈正相关,PCNA 是一种增殖标志物。Prx III 在 MCF-7 和 MDA-MB-231 乳腺癌细胞系中均有表达,并且在 MDA-MB-231 细胞中转染 siPrx III 可诱导细胞增殖抑制和细胞周期停滞。数据表明,Prx III 在细胞周期调控中具有重要作用,可能是乳腺癌中潜在的增殖标志物。

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