p27^(KIP1)和SKp2蛋白异常表达与人胶质瘤临床病理学关系的研究

Relationship between the abnormal expression of p27^(KIP1) and SKp2 proteins and clinicopathology of human glioma

目的探讨脑胶质瘤组织中p27^(KIP1)蛋白和S期激酶相关蛋白2(skp2)异常表达与临床病理因素的关系。方法应用免疫组化SP法检测45例胶质瘤和10例正常脑组织中p27^(KIP1)和Skp2蛋白表达情况。结果p27^(KIP1)和Skp2蛋白在正常脑组织和胶质瘤组织中的阳性表达率差异有显著性(P=0.033、P=0.005);p27^(KIP1)和Skp2蛋白表达水平与胶质瘤组织学分级相关(P<0.01),但与患者的性别、年龄及肿瘤大小无明显关系(P>0.05);Skp2阳性表达组和阴性表达组之间p27^(KIP1)蛋白阳性率差异有显著性(x^2=4.8458,P=0.028);胶质瘤组织中p27^(KIP1)蛋白和Skp2蛋白的表达呈负相关(r=-0.5477,P<0.05)。结论Skp2蛋白在胶质瘤组织中表达上调,加速了对p27^(KIP1)泛素化依赖的蛋白降解,使p27^(KIP1)蛋白表达降低,失去对细胞周期的调控并促进细胞异常增殖,从而参与了胶质瘤的发生和发展。

Objective To investigate the relationship between the abnormal expressions of p27^KIP1 and SKp2 proteins in human glioma tissues and clinicopathology. Methods The expression of p27^KIP1 and SKp2 proteins were examined by SP immunohistochemical staining in 45 human glioma specimens and in 10 normal human brain tissue specimens. Results There was statistically significant difference in the positive rate of p27^KIP1 and SKp2 proteins between glioma specimens and normal human brain tissues （P 〈 0. 05 ）. The expression of p27^KIP1 and SKp2 proteins was closely related with pathological grade of glioma tissues（P 〈 0. 01 ） ,but their expression in gliomas had no obvious relation to the sex, ages and sizes of tumor（ P 〉 0.05 ）. There was statistically significant difference in the positive rate of p27^KIP1 protein between the positive expression group and the negative expression group of Skp2 protein（χ^2 = 4. 8458, P = 0. 028）. There was a negative correlation between expression of p27^KIP1 and SKp2 proteins in glioma tissues （r = -0. 5477, P 〈 0. 05）. Conclusions Expression of Skp2 protein is up-regulated significantly in gliomas, and overexpression of Skp2 reduces the protein level of p27^KIP1 through ubiquitin-dependent protein degradation and causes disruption of cell cycle control and enhancement of the proliferative activity, indicating that Skp2 and p27^KIP1 play important roles in oncogenesis and development of glioma.