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
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
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DOI：
10.1073/pnas.141224998
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发表时间：
2001-07-03
影响因子：
11.1
通讯作者：
Fusco, A
中科院分区：
文献类型：
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作者：
Baldassarre, G;Fedele, M;Fusco, A
高迁移率族蛋白I-C(HMGI-C)基因的重排，包括羧基末端尾巴的丢失，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HMGI-C结构(HMCI-C/T)的转基因(TG)小鼠表现出巨大的表型，并伴有以腹部/盆腔脂肪增多为主的症状。在这里，我们报告了HMGI-C/T转基因小鼠从12个月大开始患上自然杀伤(NK)-T/NK细胞淋巴瘤。我们发现在这些淋巴瘤中IL-2和IL-15蛋白及其受体的表达增加，我们证明了HMGI-C/T蛋白在体外正向调节它们的表达。因此，HRGI-C/T介导的IL2/IL-15途径的慢性刺激可能是HMCI-C/TTG小鼠NK-T/NK细胞淋巴瘤发生的原因之一。
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 (HMCI-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 HRGI-C/T-mediated chronic stimulation of the IL2/IL-15 pathway could be responsible for the onset of NK-T/NK cell lymphomas in HMCI-C/T TG mice.