Wild-type p53 triggers a rapid senescence program in human tumor cells lacking functional p53
Wild-type p53 triggers a rapid senescence program in human tumor cells lacking functional p53
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DOI：
10.1073/pnas.94.18.9648
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发表时间：
1997-09-02
影响因子：
11.1
通讯作者：
Aaronson, SA
中科院分区：
文献类型：
--
作者：
Sugrue, MM;Shin, DY;Aaronson, SA
肿瘤抑制基因p53在决定细胞命运中起着重要的作用，肿瘤细胞中野生型p53的过表达已被证明会导致生长停滞或细胞凋亡，先前对成纤维细胞的研究为p53与衰老之间的联系提供了间接证据，本研究利用诱导型p53表达系统，发现野生型p53过表达在失去功能p53的EJ膀胱癌细胞中，触发G(1)和G(2)/M生长阻滞的快速发作，这与p21上调和有丝分裂周期蛋白（细胞周期蛋白A和B）和cdc2的抑制有关。p53诱导的生长停滞在48-72小时内是不可逆的，细胞表现出衰老表型的形态学特征以及特定的生化和超微结构标记。这些发现提供了p53过表达可以激活肿瘤细胞快速衰老的直接证据。
The p53 tumor suppressor gene has been shown to play an important role in determining cell fate, Overexpression of wild-type p53 in tumor cells has been shown to lead to growth arrest or apoptosis, Previous studies in fibroblasts have provided indirect evidence for a link between p53 and senescence, Here we show, using an inducible p53 expression system, that wild-type p53 overexpression in EJ bladder carcinoma cells, which have lost functional p53, triggers the rapid onset of G(1) and G(2)/M growth arrest associated with p21 up-regulation and repression of mitotic cyclins (cyclin A and B) and cdc2. Growth arrest in response to p53 induction became irreversible within 48-72 h, with cells exhibiting morphological features as well as specific biochemical and ultrastructural markers of the senescent phenotype. These findings provide direct evidence that p53 overexpression can activate the rapid onset of senescence in tumor cells.