SEQUENTIAL EXPRESSION OF PROTOONCOGENES DURING LECTIN-STIMULATED MITOGENESIS OF NORMAL HUMAN-LYMPHOCYTES
SEQUENTIAL EXPRESSION OF PROTOONCOGENES DURING LECTIN-STIMULATED MITOGENESIS OF NORMAL HUMAN-LYMPHOCYTES
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DOI：
10.1073/pnas.83.11.3982
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发表时间：
1986-06-01
影响因子：
11.1
通讯作者：
HOOVER, RG
中科院分区：
文献类型：
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作者：
REED, JC;ALPERS, JD;HOOVER, RG
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，IL 2）、IL 2受体（IL 2 R）和转铁蛋白受体（TFR）的基因的协调表达调节。除了生长因子及其受体外，原癌基因也可调节淋巴细胞增殖。我们使用与21种不同原癌基因同源的克隆cDNA，在用促有丝分裂凝集素植物血凝素（PHA）刺激的人外周血单核细胞（PBMC）中筛选其mRNA水平的表达，并比较了这些原癌基因mRNA积累的时间过程IL 2、IL 2 R、TFR和组蛋白H3基因的mRNA。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，我们检测到c-fos和c-myc mRNA水平在10分钟内显著增加; IL 2和IL 2 R mRNA在6小时内显著增加; c-myb、p53、N-ras和TFR mRNA在14小时内显著增加; H3 mRNA在24-36小时内显著增加。PHA刺激后c-abl、c-ets和c-yes表达逐渐增加。在PBMC中没有检测的其他原癌基因表达。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，可以消除PHA诱导的c-myb、N-ras和TFR mRNA的积累，但不能消除c-fos、c-myc、IL 2和IL 2 R mRNA的积累。这些数据表明，c-fos、c-myc、IL 2和IL 2 R属于PHA激活的PBMC中早期表达的一组基因，而c-myb、N-ras和TFR属于晚期表达的一组基因，并且c-fos和c-myc原癌基因的产物对于IL 2或IL 2 R基因的表达不是必需的。加入纯化的IL-2增强了PHA刺激的PBMC培养物中后来表达的基因c-myb、p53、N-ras和TFR的表达，以及早期基因c-myc和IL-2 R的表达，但不增强c-fos和IL-2的表达，从而表明PHA和IL-2刺激PBMC中重叠但不相同的基因组的表达。
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 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.