Discovery of deregulation of zinc homeostasis and its associated genes in esophageal squamous cell carcinoma using cDNA microarray
Discovery of deregulation of zinc homeostasis and its associated genes in esophageal squamous cell carcinoma using cDNA microarray
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DOI：
10.1002/ijc.22246
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发表时间：
2007-01-15
影响因子：
6.4
通讯作者：
Ralhan, Ranju
中科院分区：
文献类型：
--
作者：
Kumar, Anupam;Chatopadhyay, Tusharkant;Ralhan, Ranju
印度人口中的食道鳞状细胞癌(ESCC)除了与饮酒和吸烟有关外，还与营养状况差、社会经济条件低、吸烟和消费无烟烟草产品有关。为了确定这些危险因素在食管鳞癌分子发病机制中的作用，我们利用19.1K基因芯片检测了7对食管鳞癌和组织学证实的非恶性食管鳞癌组织的整体基因表达谱。最显著的发现是鉴定了19个差异表达的基因，编码与转录调控、泛素蛋白降解和维持锌稳态相关的锌结合或调节蛋白。通过实时定量RT-PCR(Real-Time QRT-PCR)验证了一组基因在食管鳞癌、异型增生和组织学非恶性食管组织中的差异表达，并使用组织芯片进行免疫组织化学分析证实了微阵列数据，证实了锌指蛋白、免疫识别细胞调节因子(c-MIR)、蜗牛同源基因2(SLUG)、锌转运蛋白、锌转运蛋白、锌代谢蛋白、金属硫蛋白MT1G的表达上调。我们还观察到MAP3K3/MEKK3、AKAP13和转谷氨酰胺酶2(TG2)的表达上调。有趣的是，我们发现在缺锌条件下生长的ESCC细胞(TE13)中，ZnT7转录上调。综上所述，我们的数据提示食管鳞癌中与锌稳态相关的基因被解除了调控。(C)2006年Wiley-Liss，Inc.
Esophageal squamous cell carcinoma (ESCC) in the Indian population is associated with poor nutritional status, low socioeconomic conditions, bidi smoking and consumption of smokeless tobacco products, besides alcohol drinking and cigarette smoking. To determine the impact of these risk factors on molecular pathogenesis of ESCC, we determined global gene expression profiles of 7 paired samples of ESCC and histologically confirmed nonmalignant esophageal tissues using 19.1K cDNA microarrays. The most salient finding was identification of 19 differentially expressed genes encoding zinc binding or modulating proteins associated with transcriptional regulation, ubiquitin-protein degradation and maintenance of zinc homeostasis. Validation of differential expression of a subset of genes by real-time quantitative RT-PCR (real-time QRT-PCR) in clinical specimens of ESCC, esophageal dysplasia and histologically nonmalignant esophageal tissues and immunohistochemical analysis using tissue microarrays confirmed the microarray data and demonstrated upregulation of zinc finger proteins, cellular modulator of immune recognition (c-MIR), snail homolog 2 (SLUG), zinc transporter, ZnT7 and downregulation of zinc metabolizing protein, metallothionein MT1G. We also observed upregulation of mitogen activated protein kinase kinase kinase 3 (MAP3K3/MEKK3), a kinase anchor protein 13 (AKAP13) and transglutaminase2 (TG2). Interestingly, we found upregulation of ZnT7 transcripts in ESCC cells (TE13) grown in zinc deficient condition. In conclusion, our data suggest deregulation of genes associated with zinc homeostasis in ESCC. (c) 2006 Wiley-Liss, Inc.