bmi-1 transgene induces lymphomas and collaborates with myc in tumorigenesis.
bmi-1 transgene induces lymphomas and collaborates with myc in tumorigenesis.
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发表时间：
1993-11
期刊：
影响因子：
8
通讯作者：
Y. Haupt;M. Bath;A. W. Harris;Jerry M. Adams
中科院分区：
文献类型：
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作者：
Y. Haupt;M. Bath;A. W. Harris;Jerry M. Adams
在E mu-myc转基因小鼠的病毒加速的B淋巴肿瘤中，bmi-1基因被发现是莫洛尼病毒插入的常见靶标，因此被认为与myc基因在淋巴瘤发生中协作，但其致癌潜力以前没有被直接测试过。为了确定bmi-1过表达是否可导致体内造血肿瘤形成，产生转基因小鼠品系，其中通过偶联的免疫球蛋白重链增强子（E mu）将bmi-1表达导向淋巴区室。虽然E mu-bmi-1转基因在B和T细胞中表达，但淋巴发育未受到干扰。然而，在具有最高表达的品系中，14%的小鼠已经发展成淋巴瘤。出乎意料的是，大多数肿瘤是T细胞谱系，虽然观察到一个B淋巴瘤病例。此外，杂交E mu-bmi-1和E mu-myc小鼠证实bmi-1转基因显著加速前B和B淋巴瘤的发作。这些结果直接表明，bmi-1可以促进T和B细胞谱系中的淋巴瘤发生，并在肿瘤发展中与myc基因协作。
The bmi-1 gene was discovered as a frequent target of Moloney virus insertion in virally accelerated B-lymphoid tumors of E mu-myc transgenic mice and hence is thought to collaborate with the myc gene in lymphomagenesis, but its oncogenic potential has not previously been tested directly. To determine whether bmi-1 overexpression can contribute to hematopoietic neoplasia in vivo, strains of transgenic mice were generated in which bmi-1 expression was directed to the lymphoid compartment by a coupled immunoglobulin heavy chain enhancer (E mu). Although the E mu-bmi-1 transgene was expressed in both B and T cells, lymphoid development was not perturbed. Nevertheless, 14% of the mice in the strain with highest expression have developed lymphoma. Unexpectedly, most tumors were of the T-cell lineage, although one case of B lymphoma was observed. Furthermore, cross breeding E mu-bmi-1 and E mu-myc mice established that the bmi-1 transgene markedly accelerated the onset of pre-B and B lymphomas. These results demonstrate directly that bmi-1 can contribute to lymphomagenesis in the T and B cell lineages and collaborate with the myc gene in tumor development.