Expression of SV40Tag, Rb and IRS-1 in glioma detected by tissue microarray and their relation with tumorigenesis and progression of gliomas / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To determine the expression of SV40Tag, Rb and IRS-1 in gliomas and to identify their function in gliomagenesis and progression.</p><p><b>METHODS</b>Tissue microarrays were constructed containing 118 samples including human glioma and meningioma, experimental glioma, and normal human brain tissue. The expression of SV40Tag, Rb, IRS-1, SV40Tag combined with Rb, and SV40Tag combined with IRS-1 were assayed by immunofluorescence or immunohistochemical techniques. The expression ratio and level were analyzed.</p><p><b>RESULTS</b>The expressions of SV40Tag, Rb and IRS-1 were detected in gliomas and benign brain tumors. Their positive expression rate in glioma was 65.9%, 64.6% and 48.8%, respectively, with a statistically non-significant difference between the malignant and benign brain tumors. The malignant degree was positively correlated with SV40Tag and IRS-1, but negatively correlated with Rb expression. The combined expression rate of SV40Tag and Rb was 51.2%, and the combined expression rate of SV40Tag and IRS-1 was 40.2%. In the normal human brain tissue only the expression of Rb (77.8%, 7/9) and IRS-1 (22.2%, 2/9) were detected, but expression of SV40Tag could not be observed.</p><p><b>CONCLUSION</b>Our findings that no expression of SV40Tag was observed in normal human brain tissue indicates that expression of SV40Tag may play an important role in the pathogenesis of glioma. It may be assumed that after SV40 virus invading human body, Rb disfunction and IRS-1 activation promote the malignant transformation of cells, which could be one of important factors in pathogenesis and procession of glioms.</p>

CDK1 expression and effects of CDK1 silencing on the malignant phenotype of glioma cells / 中华肿瘤杂志

<p><b>OBJECTIVE</b>Our previous cDNA array data have shown that expression level of CDK1 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 CDK1 expression levels in gliomas and the effects of CDK1 knockdown on phenotype of glioma cells.</p><p><b>METHODS</b>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. CDK1 expression was detected in glioma tissue array with immunohistochemical techniques. CDK1 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.</p><p><b>RESULTS</b>The expression level of CDK1 increased along with the malignancy progression of glioma in clinical specimens. The positive expression rates of CDK1 in human brain glioma tissues were 22.2% (grade I), 40.0% (grade II), 69.6% (grade III) and 78.6% (grade IV), P = 0.01, respectively. The positive expression rate of CDK1 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.</p><p><b>CONCLUSION</b>Overexpression of CDK1 may promote oncogenesis and progression of human gliomas. Downregulation of CDK1 expression can inhibit the proliferation activities of human malignant gliomas.</p>