非小细胞肺癌中Skp2的表达及其与p27蛋白表达的关系

背景与目的 S期激酶相关蛋白2(Skp2)是细胞周期正性调节因子之一,它能促进周期蛋白依赖性激酶抑制剂p27的泛索化蛋白水解,在肿瘤中过表达,本研究旨在探讨非小细胞肺癌(non-small cell lung cancerNSCLC)中Skp2表达的临床意义及其与p27蛋白表达的关系.方法应用组织芯片和免疫组织化学方法检测Skp2和p27在68例NSCLC组织和17例正常支气管上皮细胞中的表达.结果 Skp2仅在肺癌组织中表达,且与患者的组织学类型(P=0.039),肿瘤细胞的分化程度(P=0.016),性别(P=0.012)和吸烟与否(P=0.026)显著相关,而与患者的年龄和TNM分期无关.p27在正常支气管上皮细胞中均有表达,在肺癌组织中表达降低;Skp2阳性表达的患者中p27表达明显降低,两者呈负相关(P=0.021).结论 在NSCLC中,Skp2蛋白表达的增高与p27泛素化依赖的蛋白降解有关,提示Skp2蛋白过表达在NSCLC的发生和发展中可能起霞要作用.

The expression of Skp2 in human non-small cell lung cancer and its correlation with expression of p27 protein

Background and objective S-phase kinase-associated protein 2 (Skp2) is one of the positive regulators of the cell cycle that promote Ubiquitin-mediated proteolysis of the cyclin-dependent kinase inhibitor p27. Its overexpression has been implicated in tumorigenesis. In this study, we investigated the expression of Skp2 in human non- small cell lung cancer (NSCLC) and its relationship with expression of p27 protein. Methods The expression of Skp2 and p27 protein were detected in 68 NSCLC, 17 normal bronchial epithelium by the tissue chip and immunohistochemistry technology. Results Skp2 was only expressed in NSCLC patients, there was closely relationship among Skp2 expression and histological subtype, cellular differentiation, sex and smoking; Otherwise, there was no relationship among skp2 expression and age or TNM stage. The expression of p27 protein was found in normal bronchial epithelial cells, and the expression was reduced in NSCLC. The expression of p27 was significantly reduced in patients with positive expression of Skp2. Expression of Skp2 was negatively correlated with expression of p27. Conclusion The expression of Skp2 is up-regulated in NSCLC, and overexpression of Skp2 reduces the protein level of p27 through ubiquitin-dependent degradation, indicating Skp2 may play an important role in oncogenesis and development of NSCLC.