Cytoplasmic Ape1 Expression Elevated by p53 Aberration May Predict Survival and Relapse in Resected Non-Small Cell Lung Cancer
Cytoplasmic Ape1 Expression Elevated by p53 Aberration May Predict Survival and Relapse in Resected Non-Small Cell Lung Cancer
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DOI：
10.1245/s10434-012-2431-2
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发表时间：
2013-12-01
影响因子：
3.7
通讯作者：
Lee, Huei
中科院分区：
文献类型：
--
作者：
Wu, Heng-Hsiung;Chu, Ya-Chiung;Lee, Huei
背景。无嘌呤/无嘧啶核酸内切酶-1/氧化还原因子-1 (Ape1) 的亚细胞定位已被证明可通过 NF-κ B 激活促进肺肿瘤恶性肿瘤。我们假设细胞质 Ape1 表达增加可能会通过 p53 畸变导致 NF-kappa B 激活，并导致非小细胞肺癌 (NSCLC) 的不良预后。方法。在此，在各种肺癌细胞中进行E6或p53的敲低以及E6的过表达，以测试细胞质Ape1表达是否可以通过p53畸变而升高。为了检验细胞质Ape1是否与患者的预后相关，收集了125例NSCLC患者的肺部肿瘤，通过免疫组织化学和实时RT-PCR测定Ape1蛋白和mRNA的表达。结果。我们的数据表明，E6 敲低的 TL-1 细胞中细胞质 Ape1 减少，而 E6 过表达的 TL-4 和 p53 敲低 H520 细胞中细胞质 Ape1 增加；细胞侵袭能力依赖于细胞质Ape1的存在。 p53 畸变导致细胞质 Ape1 的增加可能是通过激活 Ape1 转录和 Ape1 蛋白的 S-亚硝化作用实现的。 Kaplan-Meier和Cox模型显示，与细胞质Ape1低的患者相比，细胞质Ape1高的患者的癌症特异性生存期(CSS)和无复发生存期(RFS)更短。结论。我们认为，p53 畸变导致的细胞质 Ape1 表达升高可用于预测 NSCLC 患者的不良生存和复发。
Background. Subcellular localization of apurinic/apyrimidinic endonuclease-1/redox factor-1 (Ape1) has been demonstrated to promote lung tumor malignancy via NF-kappa B activation. We hypothesized that increased cytoplasmic Ape1 expression might cause NF-kappa B activation by p53 aberration, and result in poor outcome in non-small cell lung cancer (NSCLC).Methods. Herein, knockdown of E6 or p53 and overexpression of E6 were performed in various lung cancer cells to test whether cytoplasmic Ape1 expression could be elevated by p53 aberration. To examine whether cytoplasmic Ape1 could be associated with patients' outcome, 125 lung tumors from patients with NSCLC were collected to determine Ape1 protein and mRNA expression by immunohistochemistry and real-time RT-PCR.Results. Our data showed that cytoplasmic Ape1 decreased in E6-knockdown TL-1 cells and increased in E6-overexpressed TL-4 and p53-knockdown H520 cells; and cell invasion capability was dependent on the presence of cytoplasmic Ape1. Increases in cytoplasmic Ape1 by p53 aberration may be through activation of Ape1 transcription and S-nitrosation of Ape1 protein. Kaplan-Meier and Cox models showed that patients with high cytoplasmic Ape1 had shorter cancer-specific survival (CSS) and relapse-free survival (RFS) periods than did those with low cytoplasmic Ape1.Conclusions. We suggest that cytoplasmic Ape1 expression elevated by p53 aberration may be used to predict poor survival and relapse in patients with NSCLC.