Department of Radiology, University of Texas Southwestern Medical Center, Dallas, TX 75390-8542, USA.
Oncol Rep. 2013 Jul;30(1):269-75. doi: 10.3892/or.2013.2436. Epub 2013 Apr 29.
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.
铜是细胞增殖和肿瘤血管生成所必需的。细胞内铜代谢受铜转运蛋白和伴侣蛋白网络的调节。抗氧化剂-1（ATOX1）是一种细胞溶质铜伴侣蛋白，对于细胞内铜转运至关重要，它作为细胞生长信号转导途径中的转录因子，在调节细胞增殖中发挥作用。本研究旨在通过免疫组织化学（IHC）分析非小细胞肺癌（NSCLC）组织样本中 ATOX1 的表达，探讨 ATOX1 在肺癌细胞增殖的铜相关调控中的作用，并通过评估 RNA 干扰（RNAi）介导的 ATOX1 敲低对 NSCLC 细胞中铜刺激增殖的影响来研究 ATOX1 的作用。与非恶性肺组织样本中的 ATOX1 表达相比，通过对诊断为 NSCLC 的患者的组织样本进行 IHC 分析，检测到 NSCLC 中存在 ATOX1 的过表达。通过慢病毒载体转导的短发夹 RNA（shRNA）特异性针对 ATOX1 的 NSCLC 细胞中 ATOX1 的敲低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 细胞增殖中发挥重要作用，ATOX1 可能成为针对铜代谢的肺癌治疗的治疗靶点。
