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Downregulation of CDKN2A and suppression of cyclin D1 gene expressions in malignant gliomas

BACKGROUND: Malignant gliomas are the most common in central nervous system cancer. Genome-wide association study identifies that CDKN2A was a susceptibility loci for glioma. The CDKN2A/cyclin-dependent kinase 4, 6/Retinoblastoma protein (Rb) pathway is thought to play a crucial role in malignant gliomas pathogenesis. We have investigated the expression of CDKN2A for potential correlations with malignant gliomas grade and potential role of CDKN2A on malignant gliomas pathogenesis. METHODS: Tumour tissue samples from 61 patients suffering from malignant gliomas were investigated. The expression levels of CDKN2A were detected using immunohistochemical staining and western blot. Overexpression and knockdown of CDKN2A were performed in human glioma cell lines. Subsequently, colony formation, growth curves and CDKN2A-Cyclin-Rb pathway were analyzed. RESULTS: Here we show that a lower expression of CDKN2A and a higher expression of cyclin D1 in the patients with high-grade malignant gliomas than low-grade gliomas, respectively. Moreover, overexpression of CDKN2A inhibits growth of glioma cell lines by suppression of cyclin D1 gene expression. CONCLUSIONS: Our study suggests that CDKN2A as a malignant gliomas suppressor gene, appears to be useful for predicting behaviour of high-grade malignant gliomas. CDKN2A-Cyclin-Rb pathway plays a key role on malignant gliomas formation and that therapeutic targeting of this pathway may be useful in malignant gliomas treatment

Keywords : Adult,antagonists & inhibitors,Blotting,Western,Brain Neoplasms,Cell Line,Cell Proliferation,Central Nervous System,China,Colony-Forming Units Assay,Cyclin D1,Cyclin-Dependent Kinase Inhibitor p16,Down-Regulation,Female,Gene Expression,genetics,Glioma,Growth,Humans,Immunoenzyme Techniques,Male,metabolism,methods,Middle Aged,Nervous System,pathology,Patients,Prognosis,RNA,Small Interfering,surgery,Universities,, Cdkn2a,Suppression, pars defect injection

Date of Publication : 2011 Aug 15

Authors : Liu W;Lv G;Li Y;Li L;Wang B;

Organisation : Department of Spinal Surgery, Second Xiangya Hospital, Central South University, 139 RenMin Road, Changsha, China

Journal of Publication : J Exp Clin Cancer Res

Pubmed Link : https://www.ncbi.nlm.nih.gov/pubmed/21843312

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