Haupt Y, Bath M L, Harris A W, Adams J M
Walter and Eliza Hall Institute of Medical Research, Royal Melbourne Hospital, Victoria, Australia.
Oncogene. 1993 Nov;8(11):3161-4.
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.
bmi-1基因最初是在Eμ-myc转基因小鼠的病毒加速B淋巴细胞瘤中作为莫洛尼病毒插入的常见靶点被发现的，因此被认为在淋巴瘤发生过程中与myc基因协同作用，但其致癌潜力此前尚未得到直接测试。为了确定bmi-1过表达是否会在体内导致造血系统肿瘤形成，研究人员构建了转基因小鼠品系，其中通过偶联的免疫球蛋白重链增强子（Eμ）将bmi-1的表达导向淋巴系统。尽管Eμ-bmi-1转基因在B细胞和T细胞中均有表达，但淋巴系统发育并未受到干扰。然而，在表达水平最高的品系中，有14%的小鼠发生了淋巴瘤。出乎意料的是，大多数肿瘤是T细胞系的，尽管也观察到了一例B淋巴瘤。此外，将Eμ-bmi-1和Eμ-myc小鼠进行杂交表明，bmi-1转基因显著加速了前B淋巴瘤和B淋巴瘤的发病。这些结果直接证明，bmi-1可导致T细胞和B细胞系的淋巴瘤发生，并在肿瘤发展过程中与myc基因协同作用。
