High-density oligonucleotide microarrays and functional network analysis reveal extended lung carcinogenesis pathway maps and multiple interacting genes in NNK [4-(methylnitrosamino)-1-(3-pyridyle)-1-butanone] induced CD1 mouse lung tumor
High-density oligonucleotide microarrays and functional network analysis reveal extended lung carcinogenesis pathway maps and multiple interacting genes in NNK [4-(methylnitrosamino)-1-(3-pyridyle)-1-butanone] induced CD1 mouse lung tumor
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DOI：
10.1007/s00432-006-0149-x
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发表时间：
2007-02-01
影响因子：
3.6
通讯作者：
Takano, Yasuo
中科院分区：
文献类型：
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作者：
Abdel-Aziz, Hekmat Osman;Takasaki, Ichiro;Takano, Yasuo
目的NNK[4-(methylnitrosamino)-1-(3-pyridyle)-1-butanone]是烟草烟雾中含有的一种尼古丁衍生的亚硝胺酮，是一种强化学致癌物，可用于啮齿类动物的肺癌实验模型。为了阐明其致癌机制，我们检测了22,625个小鼠基因的表达状况。方法将Affymetrix基因芯片小鼠表达430A阵列用于CD1诱导的小鼠肺癌。结果共发现876个基因在NNK诱导的肿瘤组织和正常肺组织中表达至少2倍，其中390个基因上调，486个基因下调。P值最高的功能与细胞的生长和增殖有关(P=1.71×10(-4)~4.10×10(-2))。此外，我们还确定了Wnt/β-catenin信号的典型途径(P=0.0338)。结论这些结果表明，基因表达谱的应用可能为烟草诱导的肺癌的治疗靶向提供一种更好的策略。
Purpose NNK [4-(methylnitrosamino)-1-(3-pyridyle)-1-butanone] is a nicotine-derived nitrosaminoketone contained in tobacco smoke used as a powerful chemical carcinogen for rodent experimental models of pulmonary carcinogenesis. To clarify its carcinogenetic mechanisms, we examined the expression status of 22,625 mouse genes.Methods The affymetrix GeneChip mouse expression 430 A arrays have been used in CD1-induced mouse lung tumor. The affected genes were analyzed by Ingenuity pathway analysis to investigate functional network and gene ontology.Results A total of 876 genes were found to be differentially expressed at least twofold between NNK-induced tumors and normal lung tissues, 390 up-regulated and 486 down-regulated in these lesions. The functions with the highest P values were related to cellular growth and proliferation (P = 1.71 x 10(-4) to 4.10 x 10(-2)). In addition, we identified canonical pathways for Wnt/beta-catenin signaling (P = 0.0338).Conclusions These results suggest that application of gene expression profiling may provide an improved strategy for therapeutic targeting of tobacco smoking-induced lung cancer.