Restoration of a tumorigenic phenotype by beta 2-microglobulin transfection to EL-4 mutant cells.
Restoration of a tumorigenic phenotype by beta 2-microglobulin transfection to EL-4 mutant cells.
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DOI：
10.1084/jem.175.3.843
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发表时间：
1992-03-01
期刊：
影响因子：
--
通讯作者：
Ljunggren HG
中科院分区：
文献类型：
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作者：
Glas R;Sturmhöfel K;Hämmerling GJ;Kärre K;Ljunggren HG
人们经常认为，肿瘤细胞中β2-微球蛋白(β2M)的丢失可能由于逃避免疫学识别而导致恶性进展。在这里，我们直接测试了β2M表达在肿瘤发生中的作用。从小鼠淋巴瘤EL-4中选择的β2 m缺失突变体(C4.4-25-)在正常C57B1/6(B6)小鼠中的致瘤性明显低于EL-4。成瘤性的降低与β2m的表达直接相关。转染完整的小鼠β2M基因可显著增加肿瘤的致瘤性。在裸鼠B6nu/nu中，也观察到C4.4-25-与β2m转基因细胞相比成瘤性降低，但在自然杀伤(NK)1.1阳性细胞耗尽的B6小鼠中，其致瘤性被取消。这些结果表明，恢复β2M的表达可以促进肿瘤的发生，并首次证明了通过转基因诱导主要组织相容性复合体I类的表达可以导致体内对NK细胞的逃逸。
It has frequently been suggested that loss of beta 2-microglobulin (beta 2m) in tumor cells may lead to malignant progression due to escape from immunological recognition. Here, we directly tested the role of beta 2m expression in tumorigenicity. A beta 2 m loss mutant (C4.4-25-), selected from the murine lymphoma EL-4, showed a marked reduction in tumorigenicity as compared with EL-4 in normal C57B1/6 (B6) mice. The reduced tumorigenicity was directly related to beta 2 m expression. Transfection of an intact murine beta 2m gene markedly increased the tumorigenic potential. The reduced tumorigenicity of C4.4- 25- compared with beta 2m transfected cells was observed also in athymic B6 nu/nu mice, but was abolished in B6 mice depleted of natural killer (NK) 1.1-positive cells. These results show that restoration of beta 2m expression can promote tumorigenicity and demonstrate for the first time that induction of major histocompatibility complex class I expression by transfection can lead to escape from NK cells in vivo.