通过IL-2和IL-15途径的慢性刺激，在携带截短型HMGI-C基因的转基因小鼠中发生自然杀伤细胞淋巴瘤。
Onset of natural killer cell lymphomas in transgenic mice carrying a truncated HMGI-C gene by the chronic stimulation of the IL-2 and IL-15 pathway.
作者信息
Baldassarre G, Fedele M, Battista S, Vecchione A, Klein-Szanto A J, Santoro M, Waldmann T A, Azimi N, Croce C M, Fusco A
机构信息
Kimmel Cancer Center, Jefferson Medical College, Philadelphia, PA 19107, USA.
出版信息
Proc Natl Acad Sci U S A. 2001 Jul 3;98(14):7970-5. doi: 10.1073/pnas.141224998. Epub 2001 Jun 26.
Abstract
Rearrangements of the high mobility group protein I-C (HMGI-C) gene, consisting in the loss of the carboxyl-terminal tail, have been frequently detected in benign human tumors of mesenchymal origin. We have previously demonstrated that transgenic (TG) mice carrying a truncated HMGI-C construct (HMGI-C/T) exhibit a giant phenotype together with a predominantly abdominal/pelvic lipomatosis. Here, we report that HMGI-C/T TG mice develop natural killer (NK)-T/NK cell lymphomas starting from 12 months of age. We found an increased expression of IL-2 and IL-15 proteins and their receptors in these lymphomas, and we demonstrate that HMGI-C/T protein positively regulates their expression in vitro. Therefore, the HMGI-C/T-mediated chronic stimulation of the IL-2/IL-15 pathway could be responsible for the onset of NK-T/NK cell lymphomas in HMGI-C/T TG mice.
摘要
高迁移率族蛋白I-C（HMGI-C）基因重排，表现为羧基末端尾巴缺失，在人类间充质来源的良性肿瘤中经常被检测到。我们之前已经证明，携带截短型HMGI-C构建体（HMGI-C/T）的转基因（TG）小鼠表现出巨大体型以及主要为腹部/盆腔脂肪瘤病。在此，我们报告HMGI-C/T TG小鼠从12月龄开始发生自然杀伤（NK）-T/NK细胞淋巴瘤。我们发现这些淋巴瘤中白细胞介素-2（IL-2）和白细胞介素-15（IL-15）蛋白及其受体的表达增加，并且我们证明HMGI-C/T蛋白在体外正向调节它们的表达。因此，HMGI-C/T介导的IL-2/IL-15通路的慢性刺激可能是HMGI-C/T TG小鼠中NK-T/NK细胞淋巴瘤发病的原因。
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本文引用的文献
1
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J Exp Med. 2001 Jan 15;193(2):219-31. doi: 10.1084/jem.193.2.219.
2
IL-2-induced activation-induced cell death is inhibited in IL-15 transgenic mice.在白细胞介素-15转基因小鼠中，白细胞介素-2诱导的活化诱导细胞死亡受到抑制。
Proc Natl Acad Sci U S A. 2000 Oct 10;97(21):11445-50. doi: 10.1073/pnas.200363097.
3
Viral activation of interleukin-15 (IL-15): characterization of a virus-inducible element in the IL-15 promoter region.白细胞介素-15（IL-15）的病毒激活：IL-15启动子区域中病毒诱导元件的特征
J Virol. 2000 Aug;74(16):7338-48. doi: 10.1128/jvi.74.16.7338-7348.2000.
4
The Jak-STAT pathway.Jak-STAT信号通路。
Mol Immunol. 2000 Jan-Feb;37(1-2):1-11. doi: 10.1016/s0161-5890(00)00018-3.
5
The role of high-mobility group I(Y) proteins in expression of IL-2 and T cell proliferation.高迁移率族I（Y）蛋白在白细胞介素-2表达和T细胞增殖中的作用
J Immunol. 2000 Mar 15;164(6):3157-68. doi: 10.4049/jimmunol.164.6.3157.
6
Reversible defects in natural killer and memory CD8 T cell lineages in interleukin 15-deficient mice.白细胞介素15缺陷小鼠自然杀伤细胞和记忆性CD8 T细胞谱系中的可逆性缺陷
J Exp Med. 2000 Mar 6;191(5):771-80. doi: 10.1084/jem.191.5.771.
7
The pleiotropic functions of interleukin 15: not so interleukin 2-like after all.白细胞介素15的多效性功能：终究并非那么像白细胞介素2 。
J Exp Med. 2000 Mar 6;191(5):753-6. doi: 10.1084/jem.191.5.753.
8
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9
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