Molecular Study on Differentiation-Associated Genes Involved in Both Malignant Progression of Glioma and Differentiation of Human Fetal Neural Stem Cells  

作　　者：Jun Dong Yinyan Wu Qiang Huang Fei Wang Aidong Wong Qing Lan 

机构地区：[1]Department of Neurosurgery ＆ Brain Tumor Research Laboratory, 2nd Affiliated Hospital of Suzhou University, Suozhou 215004. China

出　　处：《Chinese Journal of Clinical Oncology》2006年第6期386-391,共6页中国肿瘤临床（英文版）

基　　金：This work was supported by the NationalNatural Science Foundation of China(No. 30371457, 30400457).

摘　　要：OBJECTIVE It is unclear whether differentiation disturbances or deregulation of neural stem cells (NSCs) are the early key steps for gliomagenesis and tumor development. Furthermore, relevant molecular changes and gene-regulation pathways are unknown. This study focused on screening and validating differentiation-associated genes from both human NSCs and glioma cells with malignant progression, for the purpose of offering an experimental basis for the cellular origin of gilomas and molecular pathology of gliomagenesis. METHODS The differential-gene expression profiles of malignant progression of gliomas were established, then the differentiation related genes were screened out with a bioinformatics analysis. Expression levels of these genes was further analyzed in cultured human fetal NSCs undergoing differentiation processes with a semi-quantitative RT-PCR assay. RESULTS Eight genes were screened out from the gene-expression profiling of which the expression levels were associated with the differentiation processes of NSCs, namely CXCR4, TN-C, GLT1, IL1-RI, EGFR-8, CDC2, Ndr3 and MAPKK4. Three of them, ie., GLT1, CDC2 and MAPKK4, were further analyzed, showing that expression levels decreased with the differentiation processes of NSCs, and increased with the malignant progression of ganglioglioma. CONCLUSION Three differentiation associated genes were found negatively associated with NSCs differentiation and positively associated with malignant progression of gliomas, suggesting that differentiation disturbances of neural stem cells may be involved in oncogenesis, and that further studies on their roles in gliomagenesis should be conducted.OBJECTIVE It is unclear whether differentiation disturbances or deregulation of neural stem cells （NSCs） are the early key steps for gliomagenesis and tumor development. Furthermore, relevant molecular changes and gene-regulation pathways are unknown. This study focused on screening and validating differentiation-associated genes from both human NSCs and glioma cells with malignant progression, for the purpose of offering an experimental basis for the cellular origin of gilomas and molecular pathology of gliomagenesis. METHODS The differential-gene expression profiles of malignant progression of gliomas were established, then the differentiation related genes were screened out with a bioinformatics analysis. Expression levels of these genes was further analyzed in cultured human fetal NSCs undergoing differentiation processes with a semi-quantitative RT-PCR assay. RESULTS Eight genes were screened out from the gene-expression profiling of which the expression levels were associated with the differentiation processes of NSCs, namely CXCR4, TN-C, GLT1, IL1-RI, EGFR- 8, CDC2, Ndr3 and MAPKK4. Three of them, ie., GLT1, CDC2 and MAP- KK4, were further analyzed, showing that expression levels decreased with the differentiation processes of NSCs, and increased with the malignant progression of ganglioglioma. CONCLUSION Three differentiation associated genes were found negatively associated with NSCs differentiation and positively associated with malignant progression of gliomas, suggesting that differentiation disturbances of neural stem cells may be involved in oncogenesis, and that further studies on their roles in gliomagenesis should be conducted.

关 键 词：GLIOMA neural stem cells malignant progression differentiation. 

分 类 号：R739.4[医药卫生—肿瘤]