Reed J C, Sabath D E, Hoover R G, Prystowsky M B
Mol Cell Biol. 1985 Dec;5(12):3361-8. doi: 10.1128/mcb.5.12.3361-3368.1985.
The cellular oncogene c-myc has been implicated in the regulation of growth of normal and neoplastic cells. Recently, it was suggested that c-myc gene expression may control the G0----G1-phase transition in normal lymphocytes that were stimulated to enter the cell cycle by the lectin concanavalin A (ConA). Here we describe the effects of purified recombinant interleukin 2 (rIL2) and of ConA on levels of c-myc mRNA in the noncytolytic murine T-cell clone L2. In contrast to resting (G0) primary cultures of lymphocytes, quiescent L2 cells have a higher RNA content than resting splenocytes and express receptors for interleukin 2 (IL2). Resting L2 cells are therefore best regarded as early G1-phase cells. Purified rIL2 was found to stimulate the rapid accumulation of c-myc mRNA in L2 cells. Levels of c-myc mRNA became maximal within 1 h and declined gradually thereafter. In contrast, ConA induced slower accumulation of c-myc mRNA in L2 cells, with increased levels of c-myc mRNA becoming detectable 4 to 8 h after stimulation. Experiments with the protein synthesis inhibitor cycloheximide demonstrated that the increase in levels of c-myc mRNA that were induced by ConA was a direct effect of this lectin and not secondary to IL2 production. Cyclosporin A, an immunosuppressive agent, markedly reduced the accumulation of c-myc mRNA that was induced by ConA but only slightly diminished the accumulation of c-myc mRNA that was induced by rIL2. Taken together, these data provide evidence that (i) c-myc gene expression can be regulated by at least two distinct pathways in T lymphocytes, only one of which is sensitive to cyclosporine A, and (ii) the accumulation of c-myc mRNA can be induced in T cells by IL2 during the G1 phase of the cell cycle.
细胞癌基因c-myc与正常细胞和肿瘤细胞的生长调控有关。最近，有人提出c-myc基因表达可能控制正常淋巴细胞从G0期向G1期的转变，这些淋巴细胞被凝集素伴刀豆球蛋白A（ConA）刺激进入细胞周期。在此，我们描述了纯化的重组白细胞介素2（rIL2）和ConA对非细胞溶解性小鼠T细胞克隆L2中c-myc mRNA水平的影响。与静止（G0）的淋巴细胞原代培养物不同，静止的L2细胞比静止的脾细胞具有更高的RNA含量，并表达白细胞介素2（IL2）受体。因此，静止的L2细胞最好被视为早期G1期细胞。发现纯化的rIL2能刺激L2细胞中c-myc mRNA的快速积累。c-myc mRNA水平在1小时内达到最大值，此后逐渐下降。相比之下，ConA诱导L2细胞中c-myc mRNA的积累较慢，刺激后4至8小时可检测到c-myc mRNA水平升高。用蛋白质合成抑制剂环己酰亚胺进行的实验表明，ConA诱导的c-myc mRNA水平升高是这种凝集素的直接作用，而非继发于IL2的产生。免疫抑制剂环孢素A显著降低了ConA诱导的c-myc mRNA积累，但仅略微减少了rIL2诱导的c-myc mRNA积累。综上所述，这些数据表明：（i）c-myc基因表达在T淋巴细胞中可通过至少两条不同途径调控，其中只有一条对环孢素A敏感；（ii）在细胞周期G1期，IL2可诱导T细胞中c-myc mRNA的积累。
