Time-sensitive reversal of hyperplasia in transgenic mice expressing SV40 T antigen
Time-sensitive reversal of hyperplasia in transgenic mice expressing SV40 T antigen
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DOI：
10.1126/science.273.5280.1384
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发表时间：
1996-09-06
期刊：
影响因子：
56.9
通讯作者：
Hennighausen, L
中科院分区：
文献类型：
--
作者：
Ewald, D;Li, MG;Hennighausen, L
通过控制猴病毒40 T抗原（TAg）的表达，检测病毒癌蛋白表达在维持细胞转化中的作用作为时间的函数。从出生时起，TAg在转基因小鼠的下颌下腺中的表达诱导细胞转化和4月龄时的广泛导管增生。当TAg表达沉默3周时，增生逆转，然而，当7个月后TAg表达沉默时，即使TAg不存在，增生仍持续存在。尽管导管细胞的多倍性在4个月龄时可以逆转，但即使在TAg不存在的情况下，7个月龄的细胞仍保持多倍体。这些结果支持时间依赖性多步骤肿瘤发生的模型。其中病毒转化的细胞最终失去对病毒癌蛋白维持转化状态的依赖。
The role of viral oncoprotein expression in the maintenance of cellular transformation was examined as a function of time through controlled expression of simian virus 40 T antigen (TAg), Expression of TAg in the submandibular gland of transgenic mice from the time of birth induced cellular transformation and extensive ductal hyperplasia by 4 months of age, The hyperplasia was reversed when TAg expression was silenced for 3 weeks, When TAg expression was silenced after 7 months, however, the hyperplasia persisted even though TAg was absent, Although the polyploidy of ductal cells could be reversed at 4 months of age, cells at 7 months of age remained polyploid even in the absence of TAg, These results support a model of time-dependent multistep tumorigenesis, in which virally transformed cells eventually lose their dependence on the viral oncoprotein for maintenance of the transformed state.