Department of Gastroenterology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, Jiangsu, China.
Cell Biochem Biophys. 2013;67(3):1081-7. doi: 10.1007/s12013-013-9612-x.
Here we investigated whether the cellular accumulation of p53 protein caused by over-expression of small ubiquitin-related modifier-1 (SUMO-1) could be used as a predictive marker for prognosis in colon cancer. We detected SUMO-1 and p53 protein levels in 46 cases of colon cancer and adjacent tissues by immunohistochemistry and found that SUMO-1 was expressed at much higher levels in colon cancer compared with that in normal colon tissue. Immunoprecipitation and Western blot analysis revealed that the tumor suppressor p53 was present predominantly in the sumoylated rather than the non-sumoylated form in the colon cancer cell lines. A small interfering RNA targeted to SUMO-1 mRNA sequences was used to observe the levels of the p53 protein. Patients who showed high dual expressions of SUMO-1 and p53 tended to experience metastasis more frequently. These results suggest that the cellular accumulation of p53 protein caused by over-expression of SUMO-1 may be involved in tumor aggressiveness. Multivariate analysis confirmed that the high dual expression of SUMO-1 and p53 was an independent factor for evaluating prognosis. SUMO-1 may be useful as a novel target for therapy in colon cancer as well as a clinical indicator for tumor aggressiveness.
在这里，我们研究了通过过量表达小泛素相关修饰物 1（SUMO-1）导致的 p53 蛋白在细胞内的积累是否可以用作结肠癌预后的预测标志物。我们通过免疫组织化学检测了 46 例结肠癌和相邻组织中的 SUMO-1 和 p53 蛋白水平，发现 SUMO-1 在结肠癌中的表达水平明显高于正常结肠组织。免疫沉淀和 Western blot 分析显示，在结肠癌细胞系中，肿瘤抑制因子 p53 主要以 SUMO-1 修饰的形式而不是非 SUMO-1 修饰的形式存在。使用靶向 SUMO-1 mRNA 序列的小干扰 RNA 观察 p53 蛋白水平。显示 SUMO-1 和 p53 双重高表达的患者更容易发生转移。这些结果表明，SUMO-1 过表达导致的 p53 蛋白在细胞内的积累可能与肿瘤侵袭性有关。多变量分析证实，SUMO-1 和 p53 的双重高表达是评估预后的独立因素。SUMO-1 可能是结肠癌治疗的一个新靶点，也是评估肿瘤侵袭性的一个临床指标。
