Transcriptional profiling of non-small cell lung cancer cells with activating EGFR somatic mutations.
Transcriptional profiling of non-small cell lung cancer cells with activating EGFR somatic mutations.
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通过激活EGFR体细胞突变的非小细胞肺癌细胞的转录分析。
DOI：
10.1371/journal.pone.0001226
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发表时间：
2007-11-21
期刊：
影响因子：
3.7
通讯作者：
Kurie, Jonathan M.
中科院分区：
文献类型：
--
作者：
Choi, Kuicheon;Creighton, Chad J.;Stivers, David;Fujimoto, Nobukazu;Kurie, Jonathan M.
表皮生长因子受体（EGFR）的激活体细胞突变赋予非小细胞肺癌（NSCLC）细胞独特的生物学特征，但EGFR在该NSCLC亚组中的转录介质尚未完全阐明。在这里，我们使用遗传学和药理学的方法来阐明非小细胞肺癌细胞系的转录组。我们转录分析了一组EGFR突变型和野生型非小细胞肺癌细胞系，在存在或不存在EGFR酪氨酸激酶抑制剂的情况下培养。分层分析显示，细胞系基于EGFR突变状态（突变体与野生型）分离，并且通过监督分析鉴定表达特征，该监督分析基于突变状态（野生型与突变体）和突变类型（L 858 R与Δ746-750）区分细胞系。使用EGFR突变特异性表达特征作为探针，我们挖掘了两个独立的NSCLC患者队列的基因表达谱，并在一个子集中发现了该特征。EGFR酪氨酸激酶抑制剂治疗调节多个基因的表达，其中两个（PTGS 2和EphA 2）的蛋白产物的药理学抑制抑制EGFR突变型NSCLC细胞的锚定非依赖性生长。我们已经阐明了以前与EGFR突变型NSCLC无关的基因，其中两个增强了这些细胞的克隆形成，将这些介质与以前显示的维持细胞存活的其他介质区分开来。这些发现具有潜在的临床相关性，因为可以使用药理学工具来抑制这些基因的蛋白质产物。
Activating somatic mutations in epidermal growth factor receptor (EGFR) confer unique biologic features to non-small cell lung cancer (NSCLC) cells, but the transcriptional mediators of EGFR in this subgroup of NSCLC have not been fully elucidated. Here we used genetic and pharmacologic approaches to elucidate the transcriptomes of NSCLC cell lines. We transcriptionally profiled a panel of EGFR-mutant and -wild-type NSCLC cell lines cultured in the presence or absence of an EGFR tyrosine kinase inhibitor. Hierarchical analysis revealed that the cell lines segregated on the basis of EGFR mutational status (mutant versus wild-type), and expression signatures were identified by supervised analysis that distinguished the cell lines based on mutational status (wild-type versus mutant) and type of mutation (L858R versus Δ746-750). Using an EGFR mutation-specific expression signature as a probe, we mined the gene expression profiles of two independent cohorts of NSCLC patients and found the signature in a subset. EGFR tyrosine kinase inhibitor treatment regulated the expression of multiple genes, and pharmacologic inhibition of the protein products of two of them (PTGS2 and EphA2) inhibited anchorage-independent growth in EGFR-mutant NSCLC cells. We have elucidated genes not previously associated with EGFR-mutant NSCLC, two of which enhanced the clonogenicity of these cells, distinguishing these mediators from others previously shown to maintain cell survival. These findings have potential clinical relevance given the availability of pharmacologic tools to inhibit the protein products of these genes.
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影响因子：
158.5
作者：
Lynch, TJ;Bell, DW;Haber, DA
通讯作者：
Haber, DA
影响因子：
12.3
作者：
Creighton C;Kuick R;Misek DE;Rickman DS;Brichory FM;Rouillard JM;Omenn GS;Hanash S
通讯作者：
Hanash S
影响因子：
4.4
作者：
Kobayashi, Makiko;Saitoh, Shin-ichiroh;Miyake, Kensuke
通讯作者：
Miyake, Kensuke
影响因子：
11.2
作者：
Creighton, CJ;Hilger, AM;El-Ashry, D
通讯作者：
El-Ashry, D
影响因子：
64.8
作者：
Jeong, H;Mason, SP;Oltvai, ZN
通讯作者：
Oltvai, ZN