Knockdown of copper chaperone antioxidant-1 by RNA interference inhibits copper-stimulated proliferation of non-small cell lung carcinoma cells.
Knockdown of copper chaperone antioxidant-1 by RNA interference inhibits copper-stimulated proliferation of non-small cell lung carcinoma cells.
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DOI：
10.3892/or.2013.2436
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发表时间：
2013-07
期刊：
影响因子：
4.2
通讯作者：
Peng F
中科院分区：
文献类型：
--
作者：
Cai H;Peng F
铜是细胞增殖和肿瘤血管生成所必需的。细胞的铜代谢受铜转运体和伴侣蛋白网络的调节。抗氧化剂-1(ATOX1)是细胞内铜转运的重要伴侣蛋白，作为细胞生长信号转导途径中的转录因子，在细胞增殖调控中发挥重要作用。本研究旨在通过免疫组织化学(IHC)分析ATOX1在非小细胞肺癌(NSCLC)组织中的表达，并评价RNA干扰(RNAi)介导的ATOX1基因敲除对铜刺激的NSCLC细胞增殖的影响，以探讨ATOX1在铜相关的肺癌细胞增殖调控中的作用。对确诊为非小细胞肺癌患者的肺组织标本进行免疫组织化学分析，发现ATOX1在非小细胞肺癌组织中高表达，而在非恶性肺组织标本中检测到ATOX1的高表达。慢病毒载体转导的针对ATOX1的短发夹状RNA(ShRNA)抑制了ATOX1在NSCLC细胞中的表达，这与铜刺激的细胞增殖减少有关。这些发现表明ATOX1在铜刺激的NSCLC细胞增殖中起重要作用，ATOX1有可能成为以铜代谢为靶点的肺癌治疗靶点。
Copper is required for cell proliferation and tumor angiogenesis. Cellular copper metabolism is regulated by a network of copper transporters and chaperones. Antioxidant-1 (ATOX1) is a cytosolic copper chaperone important for intracellular copper transport, which plays a role in the regulation of cell proliferation by functioning as a transcription factor in cell growth signal-transduction pathways. The present study aimed to explore the role of ATOX1 in the copper-related regulation of lung cancer cell proliferation by immunohistochemical (IHC) analysis of ATOX1 expression in non-small cell lung cancer (NSCLC) tissue samples and by assessing the effects of RNA interference (RNAi)-mediated knockdown of ATOX1 on copper-stimulated proliferation of NSCLC cells. Overexpression of ATOX1 was detected in NSCLC by IHC analysis of the tissue samples from patients diagnosed with NSCLC when compared with expression of ATOX1 in non-malignant lung tissue samples. Knockdown of ATOX1 in the NSCLC cells transduced by a lentiviral vector encoding short hairpin RNA (shRNA) specific for ATOX1 was associated with reduction in copper-stimulated cell proliferation. These findings suggest that ATOX1 plays an important role in copper-stimulated proliferation of NSCLC cells and ATOX1 holds potential as a therapeutic target for lung cancer therapy targeting copper metabolism.
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影响因子：
4.8
作者：
Itoh, Shinichi;Kim, Ha Won;Fukai, Tohru
通讯作者：
Fukai, Tohru
影响因子：
4.8
作者：
Zhang H;Cai H;Lu X;Muzik O;Peng F
通讯作者：
Peng F
影响因子：
7.1
作者：
Uauy, R;Olivares, M;Gonzalez, M
通讯作者：
Gonzalez, M
DOI：
10.1084/jem.20111487
发表时间：
2012-02-13
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Goldberg MS;Sharp PA
通讯作者：
Sharp PA
影响因子：
56.9
作者：
Rae, TD;Schmidt, PJ;O'Halloran, TV
通讯作者：
O'Halloran, TV