CHIMERIC HOMEOBOX GENE E2A-PBX1 INDUCES PROLIFERATION, APOPTOSIS, AND MALIGNANT-LYMPHOMAS IN TRANSGENIC MICE
CHIMERIC HOMEOBOX GENE E2A-PBX1 INDUCES PROLIFERATION, APOPTOSIS, AND MALIGNANT-LYMPHOMAS IN TRANSGENIC MICE
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DOI：
10.1016/0092-8674(93)90463-z
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发表时间：
1993-09-10
期刊：
影响因子：
64.5
通讯作者：
CLEARY, ML
中科院分区：
文献类型：
--
作者：
DEDERA, DA;WALLER, EK;CLEARY, ML
在免疫球蛋白重链增强子控制下表达同源盒融合基因E2A-PBX1可有效诱导转基因小鼠的恶性肿瘤。所有动物在5个月前死亡，淋巴瘤表型与过渡性中间胸腺细胞（CD4+/CD8+/CD3med）一致。E2A-PBX1还显著改变了肿瘤前动物的淋巴细胞发育，将胸腺细胞和骨髓B系祖细胞的数量减少到正常水平的20%。尽管观察到淋巴样细胞减少，但癌前动物的循环胸腺细胞数量明显增加，但也有更高比例的细胞凋亡，表明细胞死亡增加导致明显的淋巴细胞减少。这些数据表明嵌合同源结构域蛋白E2A-PBX1矛盾地诱导淋巴样细胞增殖和凋亡，表明核癌基因诱导的细胞周期进展与程序性细胞死亡之间存在体内关联。
Expression of the homeobox fusion gene E2A-PBX1 under control of the immunoglobulin heavy chain enhancer efficiently induced malignancies in transgenic mice. All animals died before 5 months of age with lymphomas that demonstrated phenotypes consistent with transitional intermediate thymocytes (CD4+/CD8+/CD3med). E2A-PBX1 also markedly altered lymphoid development in pretumorous animals, reducing the number of thymocytes and bone marrow B lineage progenitors to 20% of normal levels. In spite of the observed reductions in lymphoid cells, premalignant animals contained significantly increased numbers of cycling thymocytes, but a higher proportion was also undergoing apoptosis, suggesting that increased cell death resulted in the marked lymphopenias. These data indicate that the chimeric homeodomain protein E2A-PBX1 paradoxically induces both proliferation and apoptosis in lymphoid cells, suggesting an in vivo association between nuclear oncogene-induced cell cycle progression and programed cell death.