CDK1 expression and effects of CDK1 silencing on the malignant phenotype of glioma cells

2007 
Objective Our previous cDNA array data have shown that expression level of CDKl increased along with the malignant progression of ganglioglioma, and decreased with the differentiation process of neural stem cells. The purpose of this study was to investigate the CDKl expression levels in gliomas and the effects of CDKl knockdown on phenotype of glioma cells. Methods Glioma tissue array was constructed, which was composed of surgical specimens of gliomas with different malignancy grades, glioma xenografts in nude mice, cellular spheroids of brain tumor stem cells, normal neural stem cells and glioma cell line. CDKl expression was detected in glioma tissue array with immunohistochemical techniques. CDKl expression in human brain glioma cell line and relevant xenogeneic graft tumor was inhibited by retroviral vectors expressing short hairpin RNAs (shRNAs). Both in vitro and in vivo changes of biological characteristics were further observed. Results The expression level of CDKl increased along with the malignancy progression of glioma in clinical specimens. The positive expression rates of CDKl in human brain glioma tissues were 22. 2% (gradeⅠ) , 40.0% (gradeⅡ) , 69.6% (gradeⅢ) and 78.6% (gradeⅣ), P = 0. 01 , respectively. The positive expression rate of CDKl in glioma cell line and implanted xenografts was similar as the clinical tumors with high malignancy, and higher than those in neural stem cells and brain tumor stem cells (P =0.0014). Expression of CDK1 was high in human fetal brain tissues and bone marrows of nude mice, but low in normal adult human brain tissues. Downregulation of CDK1 inhibited the proliferation activities notably both in SHG-44 cells in vitro and relevant xenogeneic graft tumors, and induced apoptosis of tumor cells prominantly as well. Conclusion Overexpression of CDK1 may promote oncogenesis and progression of human gliomas. Downregulation of CDK1 expression can inhibit the proliferation activities of human malignant gliomas.
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