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Global downstream pathway analysis reveals a dependence of oncogenic NF-E2-related factor 2 mutation on the mTOR growth signaling pathway.全局下游通路分析揭示致癌性 NF-E2 相关因子 2 突变依赖于 mTOR 生长信号通路。
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Nrf2 and Keap1 abnormalities in non-small cell lung carcinoma and association with clinicopathologic features.Nrf2 和 Keap1 异常与非小细胞肺癌的临床病理特征及相关性。
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NFE2L2 gene mutation in male Japanese squamous cell carcinoma of the lung.男性日本肺鳞癌中 NFE2L2 基因突变。
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肺鳞状细胞癌中RagD基因表达与NRF2突变

RagD gene expression and NRF2 mutations in lung squamous cell carcinomas.

作者信息

Sasaki Hidefumi, Shitara Masayuki, Yokota Keisuke, Hikosaka Yu, Moriyama Satoru, Yano Motoki, Fujii Yoshitaka

机构信息

Department of Oncology, Immunology and Surgery, Nagoya City University Graduate School of Medical Sciences, Nagoya, Aichi 467-8601, Japan.

出版信息

Oncol Lett. 2012 Dec;4(6):1167-1170. doi: 10.3892/ol.2012.938. Epub 2012 Sep 25.

DOI:10.3892/ol.2012.938
PMID:23226795
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3506764/
Abstract

RagD is a member of the small G protein family, which encodes a recently discovered activator of the mTOR pathway. In vitro, RagD plays an important role in the proliferation of NRF2 gene (NFE2L2) mutated cancer cells. We hypothesized that tumor RagD expression may be correlated with the mutation status of NRF2 in lung cancers. RagD mRNA levels were analyzed by quantitative real-time polymerase chain reaction (qPCR) in 90 surgically-treated lung squamous cell cancer cases, including 14 NRF2 mutation cases, and normalized by β-actin mRNA levels. Mean RagD/β-actin mRNA levels of lung squamous cell carcinoma patients did not differ with age (≤65 vs. >65), Brinkman index (<400 vs. ≥400) or gender. RagD/β-actin mRNA levels were significantly higher in stage III samples (3.204±3.623) compared to stage I samples (1.357±1.560) (P= 0.0039). In addition, higher RagD/β-actin mRNA levels were identified in NRF2 mutant samples (3.107±3.633) compared to wild-type samples (1.774±2.301) (P=0.074). These results suggest that RagD induction by NRF2 activation plays a role in the proliferation of lung squamous cell cancers.

摘要

RagD是小G蛋白家族的成员，它编码一种最近发现的mTOR通路激活剂。在体外，RagD在NRF2基因（NFE2L2）突变的癌细胞增殖中起重要作用。我们假设肿瘤RagD表达可能与肺癌中NRF2的突变状态相关。通过定量实时聚合酶链反应（qPCR）分析了90例手术治疗的肺鳞状细胞癌病例中的RagD mRNA水平，其中包括14例NRF2突变病例，并以β-肌动蛋白mRNA水平进行标准化。肺鳞状细胞癌患者的平均RagD/β-肌动蛋白mRNA水平在年龄（≤65岁与>65岁）、布林克曼指数（<400与≥400）或性别方面没有差异。与I期样本（1.357±1.560）相比，III期样本（3.204±3.623）中的RagD/β-肌动蛋白mRNA水平显著更高（P = 0.0039）。此外，与野生型样本（1.774±2.301）相比，NRF2突变样本（3.107±3.633）中的RagD/β-肌动蛋白mRNA水平更高（P = 0.074）。这些结果表明，NRF2激活诱导的RagD在肺鳞状细胞癌的增殖中起作用。