Suppression of Myc-induced apoptosis in β cells exposes multiple oncogenic properties of Myc and triggers carcinogenic progression
Suppression of Myc-induced apoptosis in β cells exposes multiple oncogenic properties of Myc and triggers carcinogenic progression
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DOI：
10.1016/s0092-8674(02)00738-9
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发表时间：
2002-05-03
期刊：
影响因子：
64.5
通讯作者：
Evan, GI
中科院分区：
文献类型：
--
作者：
Pelengaris, S;Khan, M;Evan, GI
为了探索 c-Myc 在癌发生中的作用，我们使用 c-Myc 蛋白的可切换形式开发了胰腺 β 细胞癌发生的可逆转基因模型。成年成熟 β 细胞中 c-Myc 的激活会诱导均匀的 β 细胞增殖，但伴随着压倒性的细胞凋亡，迅速侵蚀 β 细胞质量。因此，β细胞中c-Myc的致癌潜力被细胞凋亡所掩盖。在通过Bcl-X-L的共表达抑制c-Myc诱导的β细胞凋亡后，c-Myc触发快速且一致地进展为血管生成、侵袭性肿瘤。随后的 c-Myc 失活会诱导与血管变性和 β 细胞凋亡相关的快速消退。我们的数据表明，高度复杂的肿瘤性病变可以通过两个连锁分子病变的简单组合在体内诱导和维持。
To explore the role of c-Myc in carcinogenesis, we have developed a reversible transgenic model of pancreatic beta cell oncogenesis using a switchable form of the c-Myc protein. Activation of c-Myc in adult, mature beta cells induces uniform beta cell proliferation but is accompanied by overwhelming apoptosis that rapidly erodes beta cell mass. Thus, the oncogenic potential of c-Myc in beta cells is masked by apoptosis. Upon suppression of c-Myc-induced beta cell apoptosis by coexpression Of Bcl-X-L, c-Myc triggers rapid and uniform progression into angiogenic, invasive tumors. Subsequent c-Myc deactivation induces rapid regression associated with vascular degeneration and beta cell apoptosis. Our data indicate that highly complex neoplastic lesions can be both induced and maintained in vivo by a simple combination of two interlocking molecular lesions.