Chen S J, Holbrook N J, Mitchell K F, Vallone C A, Greengard J S, Crabtree G R, Lin Y
Proc Natl Acad Sci U S A. 1985 Nov;82(21):7284-8. doi: 10.1073/pnas.82.21.7284.
The gibbon leukemia cell line MLA 144 differs from every other T-lymphocyte line in that it constitutively makes interleukin 2 (IL-2) (also called T-cell growth factor) without stimulation by antigen, lectin, or tumor promoters. Previous work in which glucocorticoids were used to inhibit IL-2 production has indicated that proliferation of this cell line is dependent upon endogenously produced IL-2. We have found that the MLA 144 cell line has a copy of the gibbon leukemia virus inserted into the 3' nontranslated region of the IL-2 gene. This integration event produces a composite mRNA made up of the protein coding sequences of the IL-2 gene transcript but incorporating the viral long terminal repeat (LTR) in the 3' nontranslated region of the mRNA. This composite mRNA transcript uses the polyadenylylation signal in the viral 5' LTR and incorporates the viral transcriptional control regions. The integration event must involve only one allele of the IL-2 gene, since transcripts essentially identical to normal human IL-2 mRNA are also produced in cloned sublines of MLA 144. That the viral LTR contains a 94-base-pair repeat reminiscent of enhancer sequences in several viruses suggests that the integration of the viral LTR at the 3' end of the IL-2 gene is responsible for the constitutive production of IL-2 in the MLA 144 cell line.
长臂猿白血病细胞系MLA 144与其他所有T淋巴细胞系不同，因为它在没有抗原、凝集素或肿瘤启动子刺激的情况下，组成性地产生白细胞介素2（IL-2）（也称为T细胞生长因子）。以前使用糖皮质激素抑制IL-2产生的研究表明，该细胞系的增殖依赖于内源性产生的IL-2。我们发现MLA 144细胞系有一个长臂猿白血病病毒拷贝插入到IL-2基因的3'非翻译区。这种整合事件产生了一种复合mRNA，它由IL-2基因转录本的蛋白质编码序列组成，但在mRNA的3'非翻译区包含病毒长末端重复序列（LTR）。这种复合mRNA转录本使用病毒5' LTR中的聚腺苷酸化信号，并包含病毒转录控制区。整合事件必定只涉及IL-2基因的一个等位基因，因为在MLA 144的克隆亚系中也产生了与正常人IL-2 mRNA基本相同的转录本。病毒LTR含有一个94个碱基对的重复序列，让人联想到几种病毒中的增强子序列，这表明病毒LTR在IL-2基因3'端的整合是MLA 144细胞系中IL-2组成性产生的原因。
