Laska Magdalena J, Strandbygård Dorthe, Kjeldgaard Anette, Mains Mette, Corydon Thomas J, Memon Ashfaque A, Sørensen Boe S, Vogel Ulla, Jensen Uffe B, Nexø Bjørn A
Institute of Human Genetics, Bartholin Building, University of Aarhus, DK-8000 Aarhus C, Denmark.
Exp Cell Res. 2007 Jul 15;313(12):2611-21. doi: 10.1016/j.yexcr.2007.05.006. Epub 2007 May 22.
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-kappaB 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-kappaB-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-kappaB mediated mechanism.
RAI基因也被称为iASPP和PPP1R13L。最近的研究表明，包含RAI的区域对中青年癌症的发展很重要。据推测，RAI产物通过阻断NF-κB诱导细胞凋亡，或通过阻断p53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。在此我们报告，在通过各种方式诱导凋亡的未转化淋巴细胞和成纤维细胞中，RAI mRNA的表达增加，这些方式包括用依托泊苷、钙离子、白细胞介素-2处理和/或血清剥夺。用依托泊苷处理也增加了RAI蛋白的含量，并使其转位至细胞核。用小干扰RNA（siRNA）抑制淋巴细胞和成纤维细胞中的RAI表达可减少细胞凋亡，但用抑制NF-κB的物质柳氮磺胺吡啶处理可缓解这种依赖性。在转化细胞系HEK-293中，RAI诱导与细胞凋亡之间的关联似乎被打破。因此，我们推测RAI诱导对于未转化细胞中的细胞凋亡诱导是必要但不充分的。我们的结果可以用NF-κB介导的机制来解释。
