Engel I, Murre C
Department of Biology, University of California at San Diego, La Jolla, CA 92093-0366, USA.
Proc Natl Acad Sci U S A. 1999 Feb 2;96(3):996-1001. doi: 10.1073/pnas.96.3.996.
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.
E2A基因发生无效突变的小鼠极易自发发生胸腺淋巴瘤。为了更好地理解E2A缺陷如何促进淋巴瘤发生，我们观察了在源自E2A缺陷小鼠自发产生的淋巴瘤的细胞系中强制表达E2A基因产物E12和E47的后果。表达E2A的细胞会从引入了E47或E12的淋巴瘤培养物中逐渐被清除。表达E2A的细胞丢失的潜在机制并不涉及细胞周期进程的停滞。相反，E2A蛋白在这些淋巴瘤中激活了程序性细胞死亡途径。这种E2A介导的细胞死亡似乎在线粒体跨膜电位丧失之前发生。这些数据提供了直接证据，表明E2A基因产物可以作为肿瘤抑制因子。
