Overexpressed cyclophilin A in cancer cells renders resistance to hypoxia- and cisplatin-induced cell death
Overexpressed cyclophilin A in cancer cells renders resistance to hypoxia- and cisplatin-induced cell death
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DOI：
10.1158/0008-5472.can-06-1759
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发表时间：
2007-04-15
期刊：
影响因子：
11.2
通讯作者：
Kim, Sung Soo
中科院分区：
文献类型：
--
作者：
Choi, Kyu Jin;Piao, Yu Ji;Kim, Sung Soo
据报道，亲环素A（CypA）在癌细胞中过表达，特别是在实体瘤中。为了确定CypA在肿瘤发生中的作用，我们研究了CypA的诱导以及它在癌细胞中的作用。在这里，我们已经表明CypA的诱导与多种细胞中的缺氧相关，包括DU 145人前列腺癌细胞系。我们对CypA启动子的分析清楚地表明，CypA上调是由缺氧诱导因子-1 α转录因子介导的。有趣的是，CypA的过表达阻止了缺氧和顺铂诱导的细胞凋亡，这与抑制活性氧的产生和线粒体膜电位的去极化有关，而基于小干扰RNA的CypA敲低则加重了这些因素。这些结果表明CypA在肿瘤发生中是重要的，特别是在肿瘤细胞凋亡中。
Cyclophilin A (CypA) has been reported to be overexpressed in cancer cells, especially in solid tumors. To determine the role of CypA in tumorigenesis, we investigated the induction of CypA as well as the role it plays in cancer cells. Here, we have shown that induction of CypA is associated with hypoxia in a variety of cells, including DU145 human prostate cancer cell line. Our analysis of the CypA promoter clearly showed that CypA up-regulation is mediated by hypoxia-inducible factor-1 alpha transcription factor. Interestingly, overexpression of CypA prevented hypoxia- and cisplatin-haduced apoptosis, and this was associated with the suppression of reactive oxygen species generation and depolarization of mitochondrial membrane potential, whereas small interfering RNA-based CypA knock-down aggravated these factors. These results suggest that CypA is important in tumorigenesis; especially in tumor apoptosis.