Department of Spinal Surgery, Second Xiangya Hospital, Central South University, 139 RenMin Road, Changsha, China.
J Exp Clin Cancer Res. 2011 Aug 15;30(1):76. doi: 10.1186/1756-9966-30-76.
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.
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.
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.
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.
恶性神经胶质瘤是中枢神经系统癌症中最常见的一种。全基因组关联研究发现 CDKN2A 是神经胶质瘤的易感基因位点。CDKN2A/细胞周期蛋白依赖性激酶 4、6/视网膜母细胞瘤蛋白 (Rb) 通路被认为在恶性神经胶质瘤发病机制中起着至关重要的作用。我们研究了 CDKN2A 的表达,以潜在地与恶性神经胶质瘤的分级相关,并探讨 CDKN2A 在恶性神经胶质瘤发病机制中的潜在作用。
对 61 例患有恶性神经胶质瘤的患者的肿瘤组织样本进行了研究。采用免疫组织化学染色和 Western blot 检测 CDKN2A 的表达水平。在人神经胶质瘤细胞系中进行 CDKN2A 的过表达和敲低。随后分析集落形成、生长曲线和 CDKN2A-Cyclin-Rb 通路。
我们发现,高级别恶性神经胶质瘤患者的 CDKN2A 表达水平较低,而 cyclin D1 表达水平较高,而低级别神经胶质瘤患者则相反。此外,CDKN2A 的过表达通过抑制 cyclin D1 基因的表达抑制神经胶质瘤细胞系的生长。
我们的研究表明,CDKN2A 作为恶性神经胶质瘤的抑制基因,似乎可用于预测高级别恶性神经胶质瘤的行为。CDKN2A-Cyclin-Rb 通路在恶性神经胶质瘤的形成中起着关键作用,针对该通路的治疗可能对恶性神经胶质瘤的治疗有用。