Expression and functional role of S phase kinase associated protein 2 (Skp2) in development of glioma / 解放军医学杂志

ABSTRACT

Objective To study the expression and functional role of S phase kinase associated protein 2 (Skp2) in development of glioma. Methods Sixty surgically removed specimens of primary glioma and 4 normal brain specimens were obtained from the Department of Neurosurgery, Navy General Hospital of PLA, from June 2001 to June 2006. All the specimens were graded according to WHO Criteria as astrocytoma (grade II, n=20), anaplastic astrocytoma (grade III, n=20) and glioblastoma (grade IV, n=20). Western blotting and immunohistochemistry were used to detect the expression of Skp2 in specimens of glioma of different grades and normal brain tissue. Results Western blotting demonstrated that the expression of Skp2 in normal brain tissue was significantly lower than that in glioma specimens, and the expression increased in degree along with the elevation of malignant grade. Immunohistochemical staining showed that the Skp2 positively expressed in both the normal brain tissues and gliomas. However, Skp2 was weakly positive and mainly found in the cytoplasm in normal brain tissue and low grade glioma (grade II), while it was strongly positive and mainly observed in the nuclei in high grade glioma (grade III and IV). Furthermore, the positive expression of Skp2 was also observed in vascular endothelial cells of glioma tissue, and the glioma cells with positive Skp2 were found to gather around the vessels in glioma specimens. Statistically analysis showed that the expression of Skp2 was significantly higher in high grade glioma tissues (grade III and IV) than in normal brain tissues and low grade glioma (grade II) with significant difference (P<0.01). Conclusions Along with the increase in malignancy of glioma, the expression of Skp2 was found increasing gradually, and it transferred from cytoplasm to nuclei. Skp2 positively expressed in both vascular endothelial cells of glioma tissue and the glioma cells around vessels in glioma specimens. The change in Skp2 expression might be closely related to an increase in malignancy of glioma, the formation of new vessels, and metastasis of tumor cells.