Differential transcriptomic analysis of spontaneous lung tumors in B6C3F1 mice: comparison to human non-small cell lung cancer.
Differential transcriptomic analysis of spontaneous lung tumors in B6C3F1 mice: comparison to human non-small cell lung cancer.
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DOI：
10.1177/0192623312447543
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发表时间：
2012-12
影响因子：
1.5
通讯作者：
Hoenerhoff MJ
中科院分区：
文献类型：
--
作者：
Pandiri AR;Sills RC;Ziglioli V;Ton TV;Hong HH;Lahousse SA;Gerrish KE;Auerbach SS;Shockley KR;Bushel PR;Peddada SD;Hoenerhoff MJ
肺癌是人类癌症相关死亡的主要原因，主要是由于吸烟和氡等环境因素。国家毒理学计划（NTP）测试各种化学品和混合物的致癌危险潜力。在使用B6C3F1小鼠进行的NTP慢性生物测定中，给药和对照动物的肺肿瘤发生率仅次于肝肿瘤。为了研究化学诱导的肺肿瘤的分子机制，需要了解未经治疗的对照动物的自发性肺（SL）肿瘤中发生的遗传变化。作者评价了SL肿瘤与来自未治疗的年龄匹配动物的正常肺相比的差异转录组学变化。在SL肿瘤中，与癌症（真核起始因子2信号传导、RhoA信号传导、PTEN信号传导和哺乳动物雷帕霉素靶点信号传导）、代谢（肌醇磷酸代谢、线粒体功能障碍以及嘌呤和嘧啶代谢）和免疫应答（Fcγ R介导的吞噬作用、网格蛋白介导的内吞作用、白细胞介素8信号传导和CXCR 4信号传导）相关的几种典型途径发生了改变。对小鼠SL肿瘤和人非小细胞肺癌转录组数据集的荟萃分析显示了高度一致性。这些数据提供了关于小鼠SL肿瘤中差异转录组学变化的重要信息，这对于我们理解化学诱导的肺肿瘤至关重要，并有助于NTP 2年致癌性生物测定中的危害分析。
Lung cancer is the leading cause of cancer-related death in people and is mainly due to environmental factors such as smoking and radon. The National Toxicology Program (NTP) tests various chemicals and mixtures for their carcinogenic hazard potential. In the NTP chronic bioassay using B6C3F1 mice, the incidence of lung tumors in treated and control animals is second only to the liver tumors. In order to study the molecular mechanisms of chemically induced lung tumors, an understanding of the genetic changes that occur in spontaneous lung (SL) tumors from untreated control animals is needed. The authors have evaluated the differential transcriptomic changes within SL tumors compared to normal lungs from untreated age-matched animals. Within SL tumors, several canonical pathways associated with cancer (eukaryotic initiation factor 2 signaling, RhoA signaling, PTEN signaling, and mammalian target of rapamycin signaling), metabolism (Inositol phosphate metabolism, mitochondrial dysfunction, and purine and pyramidine metabolism), and immune responses (FcγR-mediated phagocytosis, clathrin-mediated endocytosis, interleukin 8 signaling, and CXCR4 signaling) were altered. Meta-analysis of murine SL tumors and human non–small cell lung cancer transcriptomic data sets revealed a high concordance. These data provide important information on the differential transcriptomic changes in murine SL tumors that will be critical to our understanding of chemically induced lung tumors and will aid in hazard analysis in the NTP 2-year carcinogenicity bioassays.