Chen Hai Bin, Pan Ke, Tang Mei Kuen, Chui Yiu Loon, Chen Ling, Su Zhong Jing, Shen Zhong Ying, Li En Min, Xie Wei, Lee Kenneth K H
Department of Histology and Embryology, Shantou University Medical College, Shantou, China.
Biochem Cell Biol. 2008 Aug;86(4):302-11. doi: 10.1139/o08-069.
Esophageal tumorigenesis is a complex and cascading process, involving the interaction of many genes and proteins. In this study, we have used the comparative proteomic approach to identify tumor-associated proteins and explore the carcinogenic mechanisms. Two-dimensional electrophoresis (2-DE) and MALDI-TOF MS analysis of esophageal carcinoma and control cells revealed 10 proteins that were upregulated. A further 10 proteins were downregulated. Among these 20 differentially expressed proteins, brain and reproductive organ-expressed (BRE) protein was identified as a potential tumor promoter. It was high expressed by the esophageal carcinoma cells, as confirmed by RT-PCR and immunoblotting. BRE has been reported to be a stress-responsive protein. To gain further insight into its function, BRE expression was silenced in esophageal carcinoma cells using BRE-specific small interference RNA. It was discovered that silencing BRE expression downregulated prohibitin expression, but upregulated tumor-suppressor p53 expression. Furthermore, cyclin A and CDK2 expressions were suppressed suggesting that BRE inhibited cell proliferation. These results implied that BRE plays a significant role in mediating antiapoptotic and proliferative responses in esophageal carcinoma cells.
食管肿瘤发生是一个复杂的级联过程，涉及许多基因和蛋白质的相互作用。在本研究中，我们使用比较蛋白质组学方法来鉴定肿瘤相关蛋白并探索致癌机制。对食管癌细胞和对照细胞进行二维电泳（2-DE）和基质辅助激光解吸电离飞行时间质谱（MALDI-TOF MS）分析，发现有10种蛋白表达上调。另有10种蛋白表达下调。在这20种差异表达蛋白中，脑和生殖器官表达（BRE）蛋白被鉴定为一种潜在的肿瘤促进因子。经逆转录-聚合酶链反应（RT-PCR）和免疫印迹证实，其在食管癌细胞中高表达。据报道，BRE是一种应激反应蛋白。为了进一步深入了解其功能，使用BRE特异性小干扰RNA使食管癌细胞中的BRE表达沉默。研究发现，沉默BRE表达会下调抑制素表达，但上调肿瘤抑制因子p53表达。此外，细胞周期蛋白A和细胞周期蛋白依赖性激酶2（CDK2）的表达受到抑制，这表明BRE抑制细胞增殖。这些结果表明，BRE在介导食管癌细胞的抗凋亡和增殖反应中发挥着重要作用。
