Reed J C, Alpers J D, Nowell P C, Hoover R G
Proc Natl Acad Sci U S A. 1986 Jun;83(11):3982-6. doi: 10.1073/pnas.83.11.3982.
The proliferation of non-neoplastic T lymphocytes is regulated, in part, by the coordinated expression of genes encoding T-cell growth factor (interleukin 2, IL2), IL2 receptors (IL2R), and transferrin receptors (TFR). In addition to growth factors and their receptors, protooncogenes may regulate lymphocyte proliferation. We used cloned cDNAs homologous to 21 different protooncogenes to screen for their expression at the mRNA level in human peripheral blood mononuclear cells (PBMC) stimulated with the mitogenic lectin phytohemagglutinin (PHA), and we compared the time course of accumulation of mRNAs for these protooncogenes to that of mRNAs for the IL2, IL2R, TFR, and histone H3 genes. mRNAs for c-abl, c-ets, c-yes, and N-ras were present in unstimulated PBMC. After stimulation of PBMC by PHA, we detected marked increases within 10 min in the levels of mRNA for c-fos and c-myc; within 6 hr for IL2 and IL2R mRNAs; within 14 hr for c-myb, p53, N-ras, and TFR mRNAs; and within 24-36 hr for H3 mRNA. Expression of c-abl, c-ets, and c-yes increased gradually following stimulation with PHA. None of the other protooncogenes tested was expressed in PBMC. Addition of the protein synthesis inhibitor cycloheximide, before the addition of PHA to cultures, abolished the PHA-induced accumulation of mRNAs for c-myb, N-ras, and TFR, but not of mRNAs for c-fos, c-myc, IL2, and IL2R. These data indicate that c-fos, c-myc, IL2, and IL2R belong to a group of genes expressed early, whereas c-myb, N-ras, and TFR belong to a group of genes expressed later in PHA-activated PBMC, and that the products of the c-fos and c-myc protooncogenes are not required for expression of IL2 or IL2R genes. Addition of purified IL2 augmented the expression of the later-expressed genes c-myb, p53, N-ras, and TFR in PHA-stimulated cultures of PBMC, as well as of the early genes c-myc and IL2R, but not of c-fos and IL2, thus suggesting that PHA and IL2 stimulate the expression of overlapping, but nonidentical, sets of genes in PBMC.
非肿瘤性T淋巴细胞的增殖部分受编码T细胞生长因子（白细胞介素2，IL2）、IL2受体（IL2R）和转铁蛋白受体（TFR）的基因的协调表达调控。除生长因子及其受体外，原癌基因也可能调控淋巴细胞增殖。我们使用与21种不同原癌基因同源的克隆cDNA，筛选它们在有丝分裂原凝集素植物血凝素（PHA）刺激的人外周血单个核细胞（PBMC）中mRNA水平的表达，并将这些原癌基因mRNA积累的时间进程与IL2、IL2R、TFR和组蛋白H3基因mRNA的时间进程进行比较。c-abl、c-ets、c-yes和N-ras的mRNA存在于未刺激的PBMC中。PHA刺激PBMC后，我们在10分钟内检测到c-fos和c-myc的mRNA水平显著增加；6小时内检测到IL2和IL2R的mRNA增加；14小时内检测到c-myb、p53、N-ras和TFR的mRNA增加；24 - 36小时内检测到H3的mRNA增加。PHA刺激后，c-abl、c-ets和c-yes的表达逐渐增加。测试的其他原癌基因在PBMC中均未表达。在向培养物中添加PHA之前添加蛋白质合成抑制剂环己酰亚胺，可消除PHA诱导的c-myb、N-ras和TFR的mRNA积累，但不能消除c-fos、c-myc、IL2和IL2R的mRNA积累。这些数据表明，c-fos、c-myc、IL2和IL2R属于一组早期表达的基因，而c-myb、N-ras和TFR属于一组在PHA激活的PBMC中较晚表达的基因，并且c-fos和c-myc原癌基因的产物对于IL2或IL2R基因的表达不是必需的。在PHA刺激的PBMC培养物中添加纯化的IL2可增强后期表达的基因c-myb、p53、N-ras和TFR以及早期基因c-myc和IL2R的表达，但不能增强c-fos和IL2的表达，因此表明PHA和IL2刺激PBMC中重叠但不相同的基因集的表达。
