Ectopic expression of dE2F and dDP induces cell proliferation and death in the Drosophila eye
Ectopic expression of dE2F and dDP induces cell proliferation and death in the Drosophila eye
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DOI：
10.1002/j.1460-2075.1996.tb00738.x
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发表时间：
1996-07-15
期刊：
影响因子：
11.4
通讯作者：
Dyson, N
中科院分区：
文献类型：
--
作者：
Du, W;Xie, JE;Dyson, N
E2 F活性的失调被认为有助于许多肿瘤细胞的不受控制的增殖。虽然在组织培养中已经广泛研究了过表达E2 F基因的作用，但是体内E2 F活性升高的后果是未知的。为了解决这个问题，研究了果蝇的转基因系，其中dE 2F和dDP的异位表达靶向发育中的眼睛，dDP或dE 2F的共表达破坏了正常的眼发育，导致刚毛、视锥细胞和光感受器的异常模式。dE 2F/dDP的表达引起异位的S期有丝分裂后的细胞的眼成虫盘，但没有破坏神经元分化的发病。在未定型细胞中观察到大多数S期，尽管一些已经启动感光细胞分化的细胞也被驱动进入细胞周期。细胞死亡抑制因子p35蛋白的共表达，可显著增强dE 2F/dDP依赖性表型。这些结果表明，在这种体内系统中，E2 F活性的升高可使有丝分裂后的细胞进入细胞周期，但这些细胞不能增殖，除非从凋亡中拯救出来。
The deregulation of E2F activity is thought to contribute to the uncontrolled proliferation of many tumor tells, While the effects of overexpressing E2F genes have been studied extensively in tissue culture, the consequences of elevating E2F activity in vivo are unknown, To address this issue, transgenic lines of Drosophila were studied in which ectopic expression of dE2F and dDP was targeted to the developing eye, The co-expression of dDP or dE2F disrupted normal eye development, resulting in abnormal patterns of bristles, cone cells and photoreceptors. dE2F/dDP expression caused ectopic S phases in post-mitotic cells of the eye imaginal disc but did not disrupt the onset of neuronal differentiation. Most S phases were seen in uncommitted cells, although some cells that had initiated photoreceptor differentiation were also driven into the cell cycle. Elevated expression of dE2F and dDP caused apoptosis in the eve disc, The co-expression of baculo-virus p35 protein, an inhibitor of cell death, strongly enhanced the dE2F/dDP-dependent phenotype, These results show that, in this in vivo system, the elevation of E2F activity caused post-mitotic cells to enter the cell cycle, However, these cells failed to proliferate unless rescued from apoptosis.