Deng Yanchun, Yao Libo, Chau Ling, Ng Samuel Sai-ming, Peng Ying, Liu Xinping, Au Wo-shing, Wang Jicun, Li Fuyang, Ji Shaoping, Han Hua, Nie Xiaoyan, Li Qing, Kung Hsiang-fu, Leung Suet-yi, Lin Marie Chia-mi
Department of Biochemistry and Molecular Biology, The Fourth Military Medical University, Xi'an, China.
Int J Cancer. 2003 Sep 1;106(3):342-7. doi: 10.1002/ijc.11228.
The most severe form of brain glioma, glioblastoma (GBM), is highly malignant and usually resistant to chemotherapy. Therefore, discovery of new targets for gene therapy is important. Using subtraction cloning, we identified the human N-Myc downstream-regulated gene 2 (hNDRG2), located at chromosome 14q11.2, as a gene that is significantly suppressed in GBM tissues. Semiquantitative RT-PCR showed that the hNDRG2 gene transcript is expressed in normal brain tissue and low-grade gliomas but is present at low levels in 15 of 27 (56%) human GBM tissues and all of the 6 human glioblastoma cell lines examined. Furthermore, transfection of human glioblastoma U373 and U138 cells with a cDNA encoding hNDRG2 markedly reduced the cell proliferation. Our findings provide the first evidence to suggest that hNDRG2 may play a role in glioblastoma carcinogenesis.
脑胶质瘤最严重的形式——胶质母细胞瘤(GBM),具有高度恶性,通常对化疗耐药。因此,发现新的基因治疗靶点很重要。通过消减克隆,我们鉴定出位于染色体14q11.2的人类N-Myc下游调控基因2(hNDRG2),该基因在GBM组织中显著受抑制。半定量逆转录聚合酶链反应(RT-PCR)显示,hNDRG2基因转录本在正常脑组织和低级别胶质瘤中表达,但在27例人类GBM组织中的15例(56%)以及所检测的全部6个人类胶质母细胞瘤细胞系中表达水平较低。此外,用编码hNDRG2的cDNA转染人类胶质母细胞瘤U373和U138细胞,显著降低了细胞增殖。我们的研究结果首次表明hNDRG2可能在胶质母细胞瘤的致癌过程中发挥作用。