Clinical application and functional analysis of MAGE E1 gene, glioma specific new gene belonging MAGE family

MAGE家族胶质瘤特异性新基因MAGE E1基因的临床应用及功能分析

• 批准号: 13470293
• 负责人: YOSHIMINE Toshiki
• 金额: $ 7.23万
• 依托单位: Osaka University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-13470293/
• 关键词: MAGE; Malignant glioma; proliferation; Glioblastoma; MAGE-E1; protein; MAGE-E1蛋白; グリオーマ; 細胞増殖

MAGE-E1 is a member of the melanoma-associated antigen gene (MAGE) family that is up-regulated in malignant glioma relative to normal central nervous system cells. In this manuscript, we identified MAGE-E1 protein and studied its expression in glioma cells. Antibodies were produced in three rabbits immunized with a 14-mer peptide that matched a MAGE-E1 protein segment. Western blot analysis and immunocytochemistry of U87MG cells showed the protein to be localized in the cytoplasm. The protein was enriched around the nucleus in some of U87MG cells. MAGE-E1 protein expression was high in T98G cells cultured with 10% fetal bovine serum but low in growth-arrested cells that were serum-starved for 72 hours. The expression was up-regulated by stimulation of growth-arrested cells with 20% FBS. Western blot analysis and immunohistochemistry of gliomas resected from patients showed MAGE-E1 protein to be present at higher levels in glioblastomas than in diffuse astrocytomas. Our results suggest that MAGE-E1 play a role in the proliferation of glioma cells. MAGE-E1 might be a target molecule for treatment of malignant gliomas.

MAGE-E1 是黑色素瘤相关抗原基因 (MAGE) 家族的成员，相对于正常中枢神经系统细胞，该基因在恶性神经胶质瘤中表达上调。在这份手稿中，我们鉴定了 MAGE-E1 蛋白并研究了其在神经胶质瘤细胞中的表达。在用与 MAGE-E1 蛋白片段匹配的 14 聚体肽免疫的三只兔子中产生了抗体。 U87MG 细胞的蛋白质印迹分析和免疫细胞化学显示该蛋白定位于细胞质中。该蛋白在一些 U87MG 细胞的细胞核周围富集。 MAGE-E1 蛋白在用 10% 胎牛血清培养的 T98G 细胞中表达较高，但在血清饥饿 72 小时的生长停滞细胞中表达较低。通过用 20% FBS 刺激生长停滞的细胞，表达上调。对患者切除的胶质瘤进行的蛋白质印迹分析和免疫组织化学显示，胶质母细胞瘤中的 MAGE-E1 蛋白水平高于弥漫性星形细胞瘤。我们的结果表明 MAGE-E1 在神经胶质瘤细胞的增殖中发挥作用。 MAGE-E1可能是治疗恶性胶质瘤的靶分子。

项目成果

Miura F, Yoshimine T, et al.: "Sustained release of low-dose ganciclovir from a silicone formulation prolonged the survival of rats with gliosarcomas under herpes simplex virus thymidine kinase suicide gene therapy"Gene Ther. 9・24. 1653-1658 (2002)

Miura F、Yoshimine T 等人：“硅酮制剂中低剂量更昔洛韦的持续释放延长了单纯疱疹病毒胸苷激酶自杀基因治疗下患有神经胶质肉瘤的大鼠的存活率”Gene Ther 9·24。 2002）

Miura F, Yoshimine T, et al.: "Sustained release of low-close ganeielovir from a silicone formulation prolonged the survival of rats with gliosarcomas under herpes simplex virus thymidine kinase suicide gene therapy"Gene Ther. 9・24. 1653-1658 (2002)

Miura F、Yoshimine T 等人：“硅酮制剂中低封闭加奈洛韦的持续释放延长了单纯疱疹病毒胸苷激酶自杀基因治疗下患有神经胶质肉瘤的大鼠的存活率”Gene Ther 9・24。 2002）

Izumoto S, et al.: "PTEN mutations in malignant gliomas and their relation with meningcal gliomatosis"J Neuro-Oncol. 53. 21-26 (2001)

Izumoto S 等人：“恶性神经胶质瘤中的 PTEN 突变及其与脑膜神经胶质瘤病的关系”J Neuro-Oncol。

Miura F, Yoshimine T, et al.: "Sustained release of low-dose ganciclovir from a silicone formulation prolonged the survival of rats with gliosarcomas under herpes simplex virus thymidine kinase suicide gene therapy"Gene Ther. 9(24). 1653-1658 (2002)

Miura F、Yoshimine T 等人：“从硅胶制剂中持续释放低剂量更昔洛韦可延长接受单纯疱疹病毒胸苷激酶自杀基因治疗的神经胶质肉瘤大鼠的存活时间”Gene Ther。

Izumoto S, et al.: "PTEN mutaions in malignant gliomas and their relation with meningeal careinomatosis"J Neurooncol. 53. 21-26 (2001)

Izumoto S 等人：“恶性神经胶质瘤中的 PTEN 突变及其与脑膜癌瘤病的关系”J Neurooncol。