Retrotransposition-competent human LINE-1 induces apoptosis in cancer cells with intact p53
Retrotransposition-competent human LINE-1 induces apoptosis in cancer cells with intact p53
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DOI：
10.1155/s1110724304403131
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发表时间：
2004-09-30
影响因子：
--
通讯作者：
Cannon, RE
中科院分区：
文献类型：
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作者：
Haoudi, A;Semmes, OJ;Cannon, RE
人类LINE-I(D)元件的逆转录转座是人类基因组中具有代表性的非LTR逆转录转座子，被认为是插入突变的来源之一。然而，L1逆转录转座对细胞生长和分化的影响尚不清楚。为了研究这种生物学效应的可能性以及人类L1逆转录转座对癌细胞生长的影响，我们研究了一组经过完整的逆转录转座过程后的人类L1转化细胞系。结果表明，在拥有野生型P53的人癌细胞中，L1的转座导致了P53介导的凋亡通路的激活。此外，我们发现，在L1正在进行逆转录转座的细胞中，P53的失活抑制了细胞凋亡的诱导。这表明活跃的逆转录转座和有效的P53反应之间存在关联，其中诱导细胞凋亡是主要结果。这些数据与一个模型是一致的，在该模型中，细胞将人类的逆转录转座感知为“基因损伤事件”，并且大规模的逆转录转座触发了导致细胞凋亡的信号通路。
Retrotransposition of human LINE-I (D) element, a major representative non-LTR retrotransposon in the human genome, is known to be a source of insertional mutagenesis. However, nothing is known about effects of L1 retrotransposition on cell growth and differentiation. To investigate the potential for such biological effects and the impact that human L1 retrotransposition has upon cancer cell growth, we examined a panel of human L1 transformed cell lines following a complete retrotransposition process. The results demonstrated that transposition of L1 leads to the activation of the p53-mediated apoptotic pathway in human cancer cells that possess a wild-type p53. In addition, we found that inactivation of p53 in cells, where L1 was undergoing retrotransposition, inhibited the induction of apoptosis. This suggests an association between active retrotransposition and a competent p53 response in which induction of apoptosis is a major outcome. These data are consistent with a model in which human retrotransposition is sensed by the cell as a "genetic damaging event" and that massive retrotransposition triggers signaling pathways resulting in apoptosis.