SOX4 expression in bladder carcinoma:: Clinical aspects and in vitro functional characterization
SOX4 expression in bladder carcinoma:: Clinical aspects and in vitro functional characterization
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DOI：
10.1158/0008-5472.can-05-3456
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发表时间：
2006-04-01
期刊：
影响因子：
11.2
通讯作者：
Orntoft, T
中科院分区：
文献类型：
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作者：
Aaboe, M;Birkenkamp-Demtroder, K;Orntoft, T
基于166例临床膀胱肿瘤样本和27例正常尿路上皮样本的全基因组表达谱分析，人转录因子SOX4在膀胱肿瘤中表达量比正常组织上调5倍。使用SOX4特异性抗体，我们发现癌细胞表达了SOM蛋白，因此，我们使用带有临床注释的组织微阵列对2360例膀胱肿瘤中的SOX4蛋白表达进行了评估。我们发现强SOM表达与患者生存率增加之间存在相关性（P < 0.05）。当SOX4在膀胱细胞系HU609中过表达时，SOX4强烈损害细胞活力，促进细胞凋亡。为了表征下游靶基因和SOX4诱导的途径，我们对过表达的SOX4进行了时间过程的全球表达研究。微阵列数据分析显示了130个新的som相关基因，一些涉及信号转导（MAP2K5），血管生成（NRP2）和细胞周期阻滞（PIK3R3），其他功能未知（CGI-62）。在SOX4调控的基因中，有25个在启动子序列中包含至少一个som结合基序，表明SOX4与SOX4直接结合。体外鉴定的基因组在临床膀胱材料中进行了分析，其中一小部分基因与SOM表达高度相关。目前的数据提示SOX4在膀胱癌疾病中的作用。
The human transcription factor SOX4 was 5-fold up-regulated in bladder tumors compared with normal tissue based on whole-genome expression profiling of 166 clinical bladder tumor samples and 27 normal urothelium samples. Using a SOX4-specific antibody, we found that the cancer cells expressed the SOM protein and, thus, did an evaluation of SOX4 protein expression in 2,360 bladder tumors using a tissue microarray with clinical annotation. We found a correlation (P < 0.05) between strong SOM expression and increased patient survival. When overexpressed in the bladder cell line HU609, SOX4 strongly impaired cell viability and promoted apoptosis. To characterize downstream target genes and SOX4-induced pathways, we used a time-course global expression study of the overexpressed SOX4. Analysis of the microarray data showed 130 novel SOM-related genes, some involved in signal transduction (MAP2K5), angiogenesis (NRP2), and cell cycle arrest (PIK3R3) and others with unknown functions (CGI-62). Among the genes regulated by SOX4, 25 contained at least one SOM-binding motif in the promoter sequence, suggesting a direct binding of SOX4. The gene set identified in vitro was analyzed in the clinical bladder material and a small subset of the genes showed a high correlation to SOM expression. The present data suggest a role of SOX4 in the bladder cancer disease.