Establishment of a novel neuroblastoma mouse model
Establishment of a novel neuroblastoma mouse model
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DOI：
10.3892/ijo_00000109
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发表时间：
2008-12-01
影响因子：
5.2
通讯作者：
Akamizu, Takashi
中科院分区：
文献类型：
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作者：
Iwakura, Hiroshi;Ariyasu, Hiroyuki;Akamizu, Takashi
神经母细胞瘤是最常见的儿童癌症，起源于交感神经前体。由于晚期神经母细胞瘤的预后很差，迫切需要开发新的抗癌药物。为了筛选神经母细胞瘤的治疗药物，基因工程动物模型将是有用的。为了获得巨细胞病毒启动子控制的四环素反应元件携带猴病毒40T抗原基因的转基因小鼠，我们发现一株小鼠通过T-抗EN在肾上腺中的渗漏表达而出现双侧肾上腺肿瘤。这些肾上腺肿瘤含有小而圆的肿瘤细胞，N/C比值增大，呈嗜铬粒素A和神经元特异性烯醇化酶样免疫反应。电子显微镜下可见肿瘤细胞内含有突触突起，周围有突触小泡。这些转基因小鼠的血浆多巴胺水平显著升高。MYCN在这些肿瘤中的表达水平显著升高。这些发现表明肾上腺肿瘤是一种神经母细胞瘤。这种小鼠模型将是开发化疗药物和了解神经母细胞瘤病因的有用工具。
Neuroblastoma is the most common childhood cancer, which arises from sympathetic neural precursors. Because the prognosis of advanced neuroblastoma is known to be poor, developments of new anti-cancer drugs are desperately needed. For screening of therapeutic drugs for neuroblastoma, genetically engineered animal models would be useful. In an attempt to obtain transgenic mice carrying simian virus 40 T-antigen gene under control of tetracycline responsive elements with cytomegalovirus promoter, we found one line of mice exhibiting bilateral adrenal tumors by leakage expression of T-anti-en in adrenal gland. These adrenal tumors contained small round tumor cells with increased N/C ratio, showing chromogranin A and neuron specific enolase-like immunoreactivity. By electron microscopy, tumor cells containing neuritic processes with synaptic vesicles surrounding them were observed. The plasma levels of dopamine were significantly elevated in these transgenic mice. MYCN expression levels were significantly elevated in these tumors. These findings indicated that the adrenal tumor was a neuroblastoma. This mouse model would be a useful tool for development of chemotherapeutic drugs and understanding the etiology of neuroblastoma.