Myc-mediated proliferation and lymphomagenesis, but not apoptosis, are compromised by E2F1 loss
Myc-mediated proliferation and lymphomagenesis, but not apoptosis, are compromised by E2F1 loss
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DOI：
10.1016/s1097-2765(03)00102-3
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发表时间：
2003-04-01
期刊：
影响因子：
16
通讯作者：
Cleveland, JL
中科院分区：
文献类型：
--
作者：
Baudino, TA;Maclean, KH;Cleveland, JL
MYC和E2F1促进细胞周期进程，但二者的过度表达均可引发P53依赖的细胞凋亡。在B淋巴细胞中表达Emu-Myc转基因的小鼠会患上淋巴瘤，其中大多数都存在Arf或P53肿瘤抑制基因的突变。缺乏一个或两个E2F1等位基因的EMU-MYC转基因小鼠表现出较慢的淋巴瘤发病速度，这与癌前B细胞中细胞周期蛋白依赖性激酶抑制物p27(Kip1)的表达增加和S期比例降低有关。相反，淋巴瘤中Myc诱导的细胞凋亡以及Arf和P53突变的频率不受E2F1缺失的影响。因此，Myc不需要E2F1来诱导Arf、P53或B细胞的凋亡，而是依赖于E2F1来加速细胞周期进程和下调p27(Kip1)。
Myc and E2f1 promote cell cycle progression, but overexpression of either can trigger p53-dependent apoptosis. Mice expressing an Emu-Myc transgene in B lymphocytes develop lymphomas, the majority of which sustain mutations of either the Arf or p53 tumor suppressors. Emu-Myc transgenic mice lacking one or both E2f1 alleles exhibited a slower onset of lymphoma development associated with increased expression of the cyclin-dependent kinase inhibitor p27(Kip1) and a reduced S phase fraction in precancerous B cells. In contrast, Myc-induced apoptosis and the frequency of Arf and p53 mutations in lymphomas were unaffected by E2f1 loss. Therefore, Myc does not require E2f1 to induce Arf, p53, or apoptosis in B cells, but depends upon E2f1 to accelerate cell cycle progression and downregulate p27(Kip1).