非小细胞肺癌组织中Skp2的表达及其与p27kip1和Ki-67蛋白表达的关系

目的:探讨Skp2的表达在非小细胞肺癌(nonsmallcelllungcancer,NSCLC)发生发展中的作用,及其与p27kip1和Ki67蛋白表达的关系。方法:应用免疫组化SP法检测Skp2、p27kip1和Ki67三种蛋白在60例NSCLC和20例正常支气管黏膜上皮组织中的表达。结果:NSCLC组织中Skp2蛋白表达的阳性率为48.33%(29/60),显著高于正常支气管黏膜上皮组织中的表达,P=0.000。Skp2的表达与肿瘤的组织学类型、肿瘤细胞的分化程度、TNM分期、淋巴结转移和患者吸烟与否显著相关,P值分别为0.038、0.005、0.019、0.010和0.002,但与患者的年龄及性别无关,P值分别为0.833和0.281。NSCLC组织中Skp2表达与p27kip1表达呈显著负相关,P=0.001;而与Ki67表达呈显著正相关,P=0.027。结论:Skp2在NSCLC组织中表达是上调的,可能是通过作用于细胞周期调控蛋白p27kip1,加速了对p27kip1泛素化依赖的蛋白降解,使其表达及代谢发生异常,导致细胞周期失控并促进细胞异常增殖,从而参与了NSCLC的发生和发展。

Expression of Skp2 in non-small cell lung cancer and its relationship with p27kip1 and Ki-67 protein expressions

OBJECTIVE:To investigate the expression of Skp2 and its relationship with expressions of p27~ kip1 and Ki-67 proteins in human non-small cell lung cancer(NSCLC). METHODS: Immunohistochemical methods were applied to detect the expressions of Skp2, p27~ kip1 and Ki-67 proteins in 60 surgical specimens from NSCLC patients and 20 normal bronchial epithelium. RESULTS: In NSCLC, the positive rate of Skp2 protein was 48.33%(29/60).Which was obviously higher than that in normal bronchial epithelium, P=0.000. There was no relationship between Skp2 expression and age (P=0.833) or sex (P=0.281),respectively;otherwise, there was closely relationship between Skp2 expression and histological subtype, cellular differentiation, TNM stage, lymph node metastasis, smoking, P=0.038, 0.005, 0.019, 0.010 and 0.002, respectively. Expression of Skp2 was negatively correlated with expression of p27~ kip1,P=0.001; but was positively correlated with expression of Ki-67,P=0.027. CONCLUSIONS: Expression of Skp2 is up-regulated significantly in NSCLC compared with normal bronchial epithelium,and overexpression of Skp2 reduces the protein level of p27~ kip1 through ubiquitin-dependent degradation and causes disruption of cell cycle control and enhancement of the proliferative activity, indicating Skp2 playes an important role in oncogenesis and development of NSCLC.