Mouse cDNA microarray analysis uncovers Slug targets in mouse embryonic fibroblasts
Mouse cDNA microarray analysis uncovers Slug targets in mouse embryonic fibroblasts
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DOI：
10.1016/j.ygeno.2005.09.014
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发表时间：
2006-01-01
期刊：
影响因子：
4.4
通讯作者：
Sánchez-García, I
中科院分区：
文献类型：
--
作者：
Bermejo-Rodríguez, C;Pérez-Caro, M;Sánchez-García, I
有必要揭示的机制，占正常发育和癌症的间充质表型的维护。Slug（批准的基因符号Snai 2）是锌指转录因子Snail基因家族的成员，被认为在维持非上皮表型中起作用。本研究确定了与原代小鼠胚胎成纤维细胞中Slug基因抑制相关的候选Slug靶基因。用含有15，000个克隆的小鼠cDNA微阵列（Mousechip-CNIO）进行表达分析。通过实时PCR或Western分析，共验证了15种新的Slug靶种。这些基因包括自我更新基因（Bmi 1，Nanog，Qfi 1），上皮-间充质基因（Tcfe 2a，Ctnb 1，Sin 3a，Hdac 1，Hdac 2，Muc 1，Cldn 11），存活基因（Bcl 2，Bbc 3）和细胞周期/损伤基因（Cdkn 1a，Rb 11，Mdm 2）。研究了野生型MEFs和Slug缺陷型MEFs的表达模式。Slug互补研究恢复了缺乏Slug的细胞中的异常基因表达，表明这些基因直接受Slug调控。这些结果突出了它们在介导间充质细胞中Slug功能方面的潜在作用，并可能有助于确定与Slug相关的癌症中的新型治疗生物标志物。(c)2005年爱思唯尔公司All rights reserved.
There is a need to reveal mechanisms that account for maintenance of the mesenchymal phenotype in normal development and cancer. Slug (approved gene symbol Snai2), a member of the Snail gene family of zinc-finger transcription factors, is believed to function in the maintenance of the nonepithelial phenotype. This study identified candidate Slug target genes linked to Slug gene suppression in primary mouse embryonic fibroblasts. Expression analyses were performed with a mouse cDNA microarray (Mousechip-CNIO) containing 15,000 clones. A total of 15 novel Slug target species were validated by real-time PCR or Western analyses. These included self-renewal genes (Bmi1, Nanog, Qfi1), epithelial-mesenchymal genes (Tcfe2a, Ctnb1, Sin3a, Hdac1, Hdac2, Muc1, Cldn11), survival genes (Bcl2, Bbc3), and cell cycle/damage genes (Cdkn1a, Rb11, Mdm2). Expression patterns were studied in wild-type MEFs and Slug-deficient MEFs. Slug-complementation studies recovered aberrant gene expression in cells lacking Slug, indicating that these genes were regulated directly by Slug. These results highlight their potential roles in mediating Slug function in mesenchymal cells and may help to identify novel therapeutic biomarkers in cancers linked to Slug. (c) 2005 Elsevier Inc. All rights reserved.