Ectopic expression of E47 or E12 promotes the death of E2A-deficient lymphomas
Ectopic expression of E47 or E12 promotes the death of E2A-deficient lymphomas
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DOI：
10.1073/pnas.96.3.996
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发表时间：
1999-02-02
影响因子：
11.1
通讯作者：
Murre, C
中科院分区：
文献类型：
--
作者：
Engel, I;Murre, C
E2A基因无效突变的小鼠对胸腺淋巴瘤的自发发展高度敏感。为了更好地了解E2A缺乏如何可能有助于淋巴瘤的发生，我们观察了E2A基因产物E12和E47在来自E2A缺乏小鼠自发产生的淋巴瘤的细胞系中的强制表达的后果。表达E2A的细胞从引入E47或E12的淋巴瘤培养物中稳定消除。E2A表达细胞丢失的潜在机制不涉及细胞周期进程的停滞。相反，E2A蛋白激活这些淋巴瘤中的程序性细胞死亡途径。这种E2A介导的细胞死亡似乎是由线粒体跨膜电位的损失。这些数据提供了E2A基因产物可以作为肿瘤抑制剂的直接证据。
Mice with null mutations in the E2A gene are highly susceptible to the spontaneous development of thymic lymphomas. To understand better how E2A deficiency may contribute to lymphomagenesis, we have observed the consequences of enforced expression of the E2A gene products E12 and E47 in cell lines derived from lymphomas that arose spontaneously in E2A-deficient mice. E2A-expressing cells are steadily eliminated from lymphoma cultures into which E47 or E12 was introduced. The mechanism underlying the loss of E2A-expressing cells does not involve an arrest in cell-cycle progression. Rather, the E2A proteins activate a programmed cell death pathway in these lymphomas. This E2A-mediated cell death appears to be preceded by a loss of mitochondrial transmembrane potential. These data provide direct evidence that E2A gene products can act as tumor suppressors.