Sun Qiang, Wei Xiaoluan, Feng Jie, Zhang Rong, Shen Qian, Dong Juan, Jin Yujuan, Dong Suzhen, Li Houda, Hu Yinghe
Key Laboratory of Brain Functional Genomics, Shanghai Institute of Brain Functional Genomics, East China Normal University, 200062, Shanghai, China.
Cancer Sci. 2008 Feb;99(2):234-40. doi: 10.1111/j.1349-7006.2007.00679.x.
A transgenic mouse model expressing Simian virus 40 T-antigen (SV40Tag) under the control of a tetracycline system was generated. In this model, a cerebellar tumor was developed after doxycycline hydrochloride treatment. Real time-polymerase chain reaction and immunohistochemistry results indicated that the SV40Tag gene was expressed in the tumor. Pathological analysis showed that the tumor belonged to medulloblastoma. Further molecular characterization of the tumor demonstrated that the insulin-like growth factor (IGF) signaling pathway was activated. We also found that the SV40Tag could bind and translocate insulin receptor substrate 1 into the nucleus in primary cultured tumor cells. The interaction between the IGF pathway and SV40Tag may contribute to the process of malignant transformation in medulloblastoma. This transgenic animal model provides an important tool for studies on the signal pathways involved in the preneoplastic process in medulloblastoma and could help to identify therapeutic targets for brain tumors.
构建了一种在四环素系统控制下表达猿猴病毒40大T抗原（SV40Tag）的转基因小鼠模型。在该模型中，经盐酸强力霉素处理后发生了小脑肿瘤。实时聚合酶链反应和免疫组化结果表明，SV40Tag基因在肿瘤中表达。病理分析显示该肿瘤属于髓母细胞瘤。对该肿瘤进一步的分子特征分析表明，胰岛素样生长因子（IGF）信号通路被激活。我们还发现，在原代培养的肿瘤细胞中，SV40Tag可与胰岛素受体底物1结合并使其转位至细胞核。IGF信号通路与SV40Tag之间的相互作用可能有助于髓母细胞瘤的恶性转化过程。这种转基因动物模型为研究髓母细胞瘤肿瘤发生前期过程中涉及的信号通路提供了重要工具，并有助于确定脑肿瘤的治疗靶点。
