Expression of the RAI gene is conducive to apoptosis:: Studies of induction and interference
Expression of the RAI gene is conducive to apoptosis:: Studies of induction and interference
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DOI：
10.1016/j.yexcr.2007.05.006
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发表时间：
2007-07-15
影响因子：
3.7
通讯作者：
Nexo, Bjorn A.
中科院分区：
文献类型：
--
作者：
Laska, Magdalena J.;Strandbygard, Dorthe;Nexo, Bjorn A.
RAI基因也被称为iASPP和PPP1R13L。最近的研究表明，包含RAI的区域对于年轻人和中年人的癌症发展非常重要。据推测，RAI产物通过阻断核因子-KB诱导细胞凋亡，或通过阻断P53而抑制细胞凋亡。无论哪种方式，该基因都可能影响癌前病变的存活率。在此，我们报道了不同的方法，如依托泊苷、钙离子、白介素2和/或血清剥夺等方法诱导未转化的淋巴细胞和成纤维细胞发生凋亡时，RAI mRNA的表达增加。依托泊苷处理也增加了RAI蛋白的含量，并使其移位到细胞核。用siRNA抑制淋巴细胞和成纤维细胞中RAI的表达可减少细胞凋亡，但使用核因子-KB抑制物质柳氮磺吡啶可减轻这种依赖性。在转化的HEK-293细胞系中，RAI诱导和细胞凋亡之间的联系似乎被打破。因此，我们假设RAI诱导对于未转化细胞的凋亡诱导是必要的，但不是充分的。我们的结果可以用核因子-KB介导的机制来解释。(C)2007 Elsevier Inc.保留所有权利。
The RAI gene is also known as iASPP and PPP1R13L. Recent investigations have shown that the region encompassing RAI is important for the development of cancer in young and middle-aged persons. it has been speculated that the RAI product induces apoptosis by blocking NF-KB or inhibits apoptosis by blocking p53. Either way the gene could influence the survival of precancerous lesions. Here we report that the expression of RAI mRNA was increased in non-transformed lymphocytes and fibroblasts induced to undergo apoptosis by various means, such as treatment with etoposide, calcium ions, or interleukin-2 and/or serum deprivation. Treatment with etoposide increased the content of RAI protein, too, and caused it to translocate to the nucleus. Inhibition of RAI expression in lymphocytes and fibroblasts with siRNA reduced apoptosis, but treatment with the NF-KB-inhibiting substance sulfasalazine relieved this dependence. in the transformed cell line HEK-293 the association between RAI induction and apoptosis seemed broken. Thus, we hypothesize that RAI induction is necessary but not sufficient for apoptosis induction in non-transformed cells. Our results could be explained by a NF-KB mediated mechanism. (C) 2007 Elsevier Inc. All rights reserved.