Clear cell sarcoma of the kidney: Up-regulation of neural markers with activation of the sonic hedgehog and Akt pathways
Clear cell sarcoma of the kidney: Up-regulation of neural markers with activation of the sonic hedgehog and Akt pathways
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DOI：
10.1158/1078-0432.ccr-05-1354
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发表时间：
2005-11-15
影响因子：
11.5
通讯作者：
Perlman, EJ
中科院分区：
文献类型：
--
作者：
Cutcliffe, C;Kersey, D;Perlman, EJ
目的和实验设计：肾透明细胞肉瘤（CCSK）是儿童第二常见的肾脏肿瘤，对诊断提出了重大挑战。目前尚无阳性诊断标志物，CCSK的发病机制仍是一个谜。为了解决这些挑战，14 CCSK的基因表达模式进行了比较与15个肾母细胞瘤和3个胎儿肾样本使用寡核苷酸arrays.Results：使用无监督的方法，CCSK的基因表达谱是独特的：差异表达的基因可以在很大程度上分为四类：（a）多种神经标志物，（B）Sonic hedgehog途径的成员，（c）磷酸肌醇-3-激酶/Akt细胞增殖途径的成员，和（d）已知的治疗靶点，使用Western印迹和/或免疫组织化学的关键蛋白质的相应变化证实了这些途径和蛋白质的上调。特别是，在许多CCSK中，CD 117和表皮生长因子受体在蛋白质水平上上调，提供了潜在的治疗靶点。神经标志物之一，神经生长因子受体，代表一个有前途的诊断工具CCSK.Conclusions：这项研究表明，CCSKs出现在肾间充质细胞，显示了各种各样的神经标志物。因此，它似乎对在各种其他神经外胚层和神经元肿瘤中也观察到的遗传变化敏感，包括Sonic hedgehog和磷酸肌醇-3-激酶/Akt通路的激活。CCSK中这些通路的参与暗示它们在肿瘤发生中的作用越来越大。
Purpose and Experimental Design: Clear cell sarcoma of the kidney (CCSK), the second most common renal tumor in children, poses significant diagnostic challenges. No positive diagnostic markers are available, and the pathogenesis of CCSK remains an enigma. To address these challenges, the gene expression patterns of 14 CCSKs were compared with 15 Wilms tumors and 3 fetal kidney samples using oligonucleotide arrays.Results: Using unsupervised methods, the gene expression profile of CCSK was distinctive: differentially expressed genes could largely be grouped into four categories: (a) a wide variety of neural markers, (b) members of the Sonic hedgehog pathway, (c) members of the phosphoinositide-3-kinase/Akt cell proliferation pathway, and (d) known therapeutic targets, Corresponding changes in critical proteins using Western blot and/or immunohistochemistry confirmed the up-regulation of these pathways and proteins. In particular, CD117 and epidermal growth factor receptor are up-regulated at the protein,level in many CCSKs, providing potential therapeutic targets. One of the neural markers, nerve growth factor receptor, represents a promising diagnostic tool for CCSK.Conclusions: This study suggests that CCSKs arise within a renal mesenchymal cell that shows a wide variety of neural markers. As such, it seems to be susceptible to genetic changes also seen in a variety of other neuroectodermal and neuronal tumors, including activation of Sonic hedgehog and phosphoinositide-3-kinase/Akt pathways. Involvement of these pathways in CCSKs implicates their widening role in tumorigenesis.