Differential disruption of cell cycle pathways in small cell and non-small cell lung cancer.
Differential disruption of cell cycle pathways in small cell and non-small cell lung cancer.
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DOI：
10.1038/sj.bjc.6603167
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发表时间：
2006-06-19
影响因子：
8.8
通讯作者：
中科院分区：
文献类型：
--
作者：
肺癌是世界上癌症相关死亡率的主要原因，其中小细胞肺癌（SCLC）和非小细胞肺癌（NSCLC）包括两种主要细胞类型。虽然这些细胞类型可以很容易地区分在组织学水平上，其潜在的分子差异的知识是非常有限的。在这项研究中，我们比较了14个小细胞肺癌细胞系对27个非小细胞肺癌细胞系使用集成阵列比较基因组杂交和基因表达谱的方法，以确定亚型特异性中断。使用严格的标准，我们已经确定了159个负责这些细胞类型的不同生物学的基因。这些基因的生物学功能排序揭示了细胞周期途径中的关键成分的差异破坏。我们新的比较组合基因组和转录组分析不仅确定了差异改变的基因，而且还揭示了某些共享的途径在这些细胞类型的不同步骤中优先被破坏。小细胞肺癌表现出MRP5表达增加，Wnt通路抑制剂激活，p38 MAPK激活基因上调，而NSCLC表现出CDKN2A下调，MAPK 9和EGFR上调。这些信息表明，SCLC和NSCLC中的细胞周期上调通过截然不同的机制发生，突出了在这些癌症的治疗中需要差异化的分子靶点选择。
Lung cancer is the leading cause of cancer-related mortality in the world, with small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC) comprising the two major cell types. Although these cell types can be distinguished readily at the histological level, knowledge of their underlying molecular differences is very limited. In this study, we compared 14 SCLC cell lines against 27 NSCLC cell lines using an integrated array comparative genomic hybridisation and gene expression profiling approach to identify subtype-specific disruptions. Using stringent criteria, we have identified 159 of the genes that are responsible for the different biology of these cell types. Sorting of these genes by their biological functions revealed the differential disruption of key components involved in cell cycle pathways. Our novel comparative combined genome and transcriptome analysis not only identified differentially altered genes, but also revealed that certain shared pathways are preferentially disrupted at different steps in these cell types. Small cell lung cancer exhibited increased expression of MRP5, activation of Wnt pathway inhibitors, and upregulation of p38 MAPK activating genes, while NSCLC showed downregulation of CDKN2A, and upregulation of MAPK9 and EGFR. This information suggests that cell cycle upregulation in SCLC and NSCLC occurs through drastically different mechanisms, highlighting the need for differential molecular target selection in the treatment of these cancers.
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影响因子：
64.8
作者：
Ishitani, T;Ninomiya-Tsuji, J;Matsumoto, K
通讯作者：
Matsumoto, K
小细胞肺癌的特征是染色体3p，4q，5q，10q，10q，13q和17p的缺失发生率很高。
影响因子：
8.8
作者：
Petersen, I;Langreck, H;Wolf, G;Schwendel, A;Psille, R;Vogt, P;Reichel, M B;Ried, T;Dietel, M
通讯作者：
Dietel, M
影响因子：
4.4
作者：
Jin, DY;Kozak, CA;Jeang, KT
通讯作者：
Jeang, KT
影响因子：
254.7
作者：
Parkin, DM;Bray, F;Pisani, P
通讯作者：
Pisani, P
影响因子：
3.7
作者：
Coe, BR;Lee, EHL;Lam, WL
通讯作者：
Lam, WL