Expression profiling of epithelial plasticity in tumor progression
Expression profiling of epithelial plasticity in tumor progression
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DOI：
10.1038/sj.onc.1206887
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发表时间：
2003-10-16
期刊：
影响因子：
8
通讯作者：
Kraut, N
中科院分区：
文献类型：
--
作者：
Jechlinger, M;Grunert, S;Kraut, N
上皮细胞向间质细胞转化（Epithelial-to-mesenchymal transition，EMT）是上皮细胞向成纤维细胞转化的过程，是恶性肿瘤发生、发展和转移的重要环节。为了鉴定参与EMT和转移的分子参与者，我们进行了表达pro。基于克隆的、完全极化的乳腺上皮细胞，建立了一组组合的体外/体内细胞模型。使用了7个密切相关的细胞对，这些细胞对被定义的癌基因和/或外部因素修饰，并显示出与细胞迁移、局部侵袭和转移相关的上皮可塑性的特定方面。由于mRNA水平不一定反映细胞中的蛋白质水平，我们使用了改进的表达蛋白。基于多聚体结合RNA的LING方法，适用于分析Affyphin芯片上的全局基因表达。所有受调控的基因中有相当一部分被发现在翻译水平上受到专门控制。更多，亲。对上述多个细胞对的分类允许人们通过聚类分析鉴定少量基因，特别是将基因表达与EMT、转移、分散和/或癌基因功能相关联。在EMT期间特异性调控的一小组基因被鉴定，包括参与细胞增殖、上皮极性、存活和转分化为具有侵袭行为的间充质样细胞的关键调控因子和信号通路。
Epithelial-to-mesenchymal transition (EMT), a switch of polarized epithelial cells to a migratory, fibroblastoid phenotype, is increasingly considered as an important event during malignant tumor progression and metastasis. To identify molecular players involved in EMT and metastasis, we performed expression pro. ling of a set of combined in vitro/in vivo cellular models, based on clonal, fully polarized mammary epithelial cells. Seven closely related cell pairs were used, which were modified by defined oncogenes and/or external factors and showed specific aspects of epithelial plasticity relevant to cell migration, local invasion and metastasis. Since mRNA levels do not necessarily reflect protein levels in cells, we used an improved expression pro. ling method based on polysome-bound RNA, suitable to analyse global gene expression on Affymetrix chips. A substantial fraction of all regulated genes was found to be exclusively controlled at the translational level. Further more, pro. ling of the above multiple cell pairs allowed one to identify small numbers of genes by cluster analysis, specifically correlating gene expression with EMT, metastasis, scattering and/or oncogene function. A small set of genes specifically regulated during EMT was identified, including key regulators and signaling pathways involved in cell proliferation, epithelial polarity, survival and trans-differentiation to mesenchymal-like cells with invasive behavior.