Impact of the p53 status of tumor cells on extrinsic and intrinsic apoptosis signaling.
Impact of the p53 status of tumor cells on extrinsic and intrinsic apoptosis signaling.
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DOI：
10.1186/1478-811x-11-27
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发表时间：
2013-04-17
期刊：
影响因子：
--
通讯作者：
Ehrhardt H
中科院分区：
文献类型：
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作者：
Wachter F;Grunert M;Blaj C;Weinstock DM;Jeremias I;Ehrhardt H
p53蛋白是人类癌症中研究最好的靶点。几十年来，人们一直认为p53主要作为肿瘤抑制因子并通过转录调节发挥作用。直到最近，p53复杂多样的功能才引起了更多的关注。使用几种分子方法，我们研究了不同的p53变体对外源性和内源性凋亡信号的影响。我们复制了先前发表的内在凋亡诱导的结果：野生型p53促进细胞死亡，不同的p53突变降低凋亡敏感性。预测p53状态对外源性细胞死亡诱导的影响要复杂得多。肿瘤细胞系和原发性异种移植肿瘤细胞中p53的存在导致细胞死亡增加、不变或减少。突变型p53取代野生型p53不影响外源性凋亡诱导能力。总之，我们已经确定了p53对外源性细胞死亡诱导的非预期影响。我们建议，肿瘤细胞的p53状态对外源性凋亡信号的影响应详细研究，特别是在治疗方法的背景下，旨在恢复p53功能，以促进细胞死亡通过外源性凋亡途径。
The p53 protein is the best studied target in human cancer. For decades, p53 has been believed to act mainly as a tumor suppressor and by transcriptional regulation. Only recently, the complex and diverse function of p53 has attracted more attention. Using several molecular approaches, we studied the impact of different p53 variants on extrinsic and intrinsic apoptosis signaling. We reproduced the previously published results within intrinsic apoptosis induction: while wild-type p53 promoted cell death, different p53 mutations reduced apoptosis sensitivity. The prediction of the impact of the p53 status on the extrinsic cell death induction was much more complex. The presence of p53 in tumor cell lines and primary xenograft tumor cells resulted in either augmented, unchanged or reduced cell death. The substitution of wild-type p53 by mutant p53 did not affect the extrinsic apoptosis inducing capacity. In summary, we have identified a non-expected impact of p53 on extrinsic cell death induction. We suggest that the impact of the p53 status of tumor cells on extrinsic apoptosis signaling should be studied in detail especially in the context of therapeutic approaches that aim to restore p53 function to facilitate cell death via the extrinsic apoptosis pathway.