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首页> 外文期刊>Cell cycle >Aurora A is differentially expressed in gliomas, is associated with patient survival in glioblastoma, and is a potential chemotherapeutic target in gliomas
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Aurora A is differentially expressed in gliomas, is associated with patient survival in glioblastoma, and is a potential chemotherapeutic target in gliomas

机译：Aurora A在神经胶质瘤中差异表达，与胶质母细胞瘤患者的生存相关，并且是神经胶质瘤中潜在的化疗靶标

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Aurora A is critical for mitosis and is overexpressed in several neoplasms. Its overexpression transforms cultured cells, and both its overexpression and knockdown cause genomic instability. In transgenic mice, Aurora A haploinsufficiency, not overexpression, leads to increased malignant tumor formation. Aurora A thus appears to have both tumor-promoting and tumor-suppressor functions. Here, we report that Aurora A protein, measured by quantitative western blotting, is differentially expressed in major glioma types in lineage-specific patterns. Aurora A protein levels in WHO grade II oligodendrogliomas (n = 16) and grade III anaplastic oligodendrogliomas (n = 16) are generally low, similar to control epilepsy cerebral tissue (n = 11). In contrast, pilocytic astrocytomas (n = 6) and ependymomas (n = 12) express high Aurora A levels. Among grade II to grade III astrocytomas (n = 7, n = 14, respectively) and grade IV glioblastomas (n = 31), Aurora A protein increases with increasing tumor grade. We also found that Aurora A expression is induced by hypoxia in cultured glioblastoma cells and is overexpressed in hypoxic regions of glioblastoma tumors. Retrospective Kaplan-Meier analysis revealed that both lower Aurora A protein measured by quantitative western blot (n = 31) and Aurora A mRNA levels measured by real-time quantitative RT-PCR (n = 58) are significantly associated with poorer patient survival in glioblastoma. Furthermore, we report that the selective Aurora A inhibitor MLN8237 is potently cytotoxic to glioblastoma cells, and that MLN8237 cytotoxicty is potentiated by ionizing radiation. MLN8237 also appeared to induce senescence and differentiation of glioblastoma cells. Thus, in addition to being significantly associated with survival in glioblastoma, Aurora A is a potential new drug target for the treatment of glioblastoma and possibly other glial neoplasms.
机译：极光A对有丝分裂至关重要，在几种肿瘤中过表达。它的过表达转化了培养的细胞，其过表达和敲低都导致基因组不稳定。在转基因小鼠中，极光A单倍体不足而不是过度表达会导致恶性肿瘤形成增加。因此，极光A似乎同时具有促进肿瘤和抑制肿瘤的功能。在这里，我们报告通过定量蛋白质印迹法测量的Aurora A蛋白在主要神经胶质瘤类型中以谱系特异性模式差异表达。 WHO II级少突神经胶质瘤（n = 16）和III级间变性少突神经胶质瘤（n = 16）中的Aurora A蛋白水平通常较低，类似于对照癫痫脑组织（n = 11）。相反，毛细胞星形细胞瘤（n = 6）和室管膜瘤（n = 12）表现出高的Aurora A水平。在II级至III级星形细胞瘤（分别为n = 7，n = 14）和IV级胶质母细胞瘤（n = 31）中，Aurora A蛋白随着肿瘤等级的增加而增加。我们还发现，在培养的胶质母细胞瘤细胞中缺氧诱导了Aurora A的表达，并且在胶质母细胞瘤肿瘤的缺氧区域中过表达。回顾性Kaplan-Meier分析显示，通过定量蛋白质印迹法测定的较低Aurora A蛋白（n = 31）和通过实时定量RT-PCR测定的Aurora A mRNA水平（n = 58）均与胶质母细胞瘤患者较差的存活率显着相关。此外，我们报告说，选择性Aurora A抑制剂MLN8237对胶质母细胞瘤细胞有强烈的细胞毒性，而电离辐射可增强MLN8237的细胞毒性。 MLN8237也似乎诱导胶质母细胞瘤细胞的衰老和分化。因此，除了与胶质母细胞瘤的存活显着相关之外，极光A是治疗胶质母细胞瘤和可能的其他神经胶质瘤的潜在新药靶标。

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