SOX2 identified as a target gene for the amplification at 3q26 that is frequently detected in esophageal squamous cell carcinoma
SOX2 identified as a target gene for the amplification at 3q26 that is frequently detected in esophageal squamous cell carcinoma
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DOI：
10.1016/j.cancergencyto.2010.01.023
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发表时间：
2010-10-15
影响因子：
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通讯作者：
Yoshikawa, Toshikazu
中科院分区：
文献类型：
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作者：
Gen, Yasuyuki;Yasui, Kohichiroh;Yoshikawa, Toshikazu
SOX 2是一种具有高迁移率族DNA结合结构域的转录因子，在胚胎发生和器官发生期间作为主调节因子发挥作用。我们研究了DNA拷贝数畸变在食管鳞状细胞癌（ESCC）细胞系使用高密度寡核苷酸芯片，发现在染色体区域3q26频繁扩增。扩增的最小重叠区域的估计范围为1.3 Mb。这个染色体区域包括一个单一的基因，SOX 2。SOX 2蛋白在该基因被扩增的细胞系中过表达。敲除实验表明，SOX 2促进ESCC细胞的增殖。通过表达阵列分析结合小干扰RNA细胞转染研究确定可能受SOX 2调节的基因。在40例原发性ESCC中的6例（15%）中观察到SOX 2拷贝数增加（> 2倍）。免疫组化研究显示，SOX 2蛋白的表达显着升高，在62的89个ESCC肿瘤（70%），与他们的非肿瘤性对应物相比，和SOX 2的表达上调与ESCC的分化差。我们的研究结果表明，SOX 2可能是3q26扩增的靶点，因此可能参与ESCC的发生或进展。(C)2010年爱思唯尔公司All rights reserved.
SOX2 is a transcription factor with a high-mobility group DNA-binding domain that functions as a master regulator during embryogenesis and organogenesis. We investigated DNA copy number aberrations in esophageal squamous cell carcinoma (ESCC) cell lines using a high-density oligonucleotide microarray and found frequent amplification at the chromosomal region 3q26. The estimated extent of the minimal overlapping region of amplification was 1.3 Mb. This chromosomal region includes a single gene, SOX2. The SOX2 protein was overexpressed in cell lines in which the gene was amplified. Knockdown experiments showed that SOX2 promotes proliferation of ESCC cells. Genes potentially modulated by SOX2 were determined by expression array analyses combined with small interfering RNA cell-transfection studies. A copy number gain of SOX2 (> 2-fold) was observed in 6 of the 40 primary ESCCs (15%). Immunohistochemical study revealed that expression of the SOX2 protein was significantly elevated in 62 of the 89 ESCC tumors (70%), compared with their nontumorous counterparts, and that upregulated expression of SOX2 was associated with poor differentiation of ESCC. Our results suggest that SOX2 is likely to be a target of the 3q26 amplification and may therefore be involved in the development or progression of ESCC. (C) 2010 Elsevier Inc. All rights reserved.