Regulation of c-myc mRNA levels in normal human lymphocytes by modulators of cell proliferation.
Regulation of c-myc mRNA levels in normal human lymphocytes by modulators of cell proliferation.
复制标题
通过细胞增殖调节剂调节正常人淋巴细胞中的 c-myc mRNA 水平。
DOI：
10.1073/pnas.82.12.4221
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发表时间：
1985
影响因子：
11.1
通讯作者：
Hoover,RG
中科院分区：
文献类型：
--
作者：
Reed,JC;Nowell,PC;Hoover,RG
细胞癌基因c-myc的表达增加最近已被证明在某些类型的增殖非肿瘤细胞，包括凝集素促分裂原刺激的淋巴细胞，这表明该原癌基因在正常细胞的生长调节的作用。在这里，我们报告了几种调节淋巴细胞增殖的人外周血单个核细胞（PBMC）的c-myc mRNA的稳态水平的影响。用凝集素促分裂原植物血凝素（PHA）、佛波酯佛波12-肉豆蔻酸酯13-乙酸酯、钙离子载体离子霉素或单克隆抗体OKT 3刺激PBMC（抗抗原受体复合物）在3小时内产生c-myc mRNA水平的显著增加。（rIL-2; Cetus）对c-myc表达的影响很小，但与PHA联合，在PHA刺激的培养物中加入各种淋巴细胞增殖的抑制剂显示，环孢菌素A，地塞米松，OKT 11 A抗体（抗绵羊红细胞受体）降低了在3小时和24小时测量的c-myc mRNA水平，而抗Tac因此，环孢菌素A、地塞米松和OKT 11 A干扰T细胞活化的早期事件，而抗Tac作用较晚。羟基脲和42/6抗体（抗转铁蛋白受体），这损害了G1-S转换在循环细胞，未能抑制c-myc的表达，而是延迟c-myc mRNA水平的下降，通常发生的DNA合成的开始。这些数据表明c-myc在细胞周期的几个点受到调节（在正常淋巴细胞中）。
Increased expression of the cellular oncogene c-myc has recently been demonstrated in some types of proliferating non-neoplastic cells, including lectin mitogen-stimulated lymphocytes, suggesting a role for this protooncogene in the regulation of growth of normal cells. Here we report the effects of several modulators of lymphocyte proliferation on the steady-state levels of c-myc mRNA in human peripheral blood mononuclear cells (PBMC). Stimulating PBMC with lectin mitogen phytohemagglutinin (PHA), phorbol ester phorbol 12-myristate 13-acetate, calcium ionophore ionomycin, or monoclonal antibody OKT3 (anti-antigen receptor complex) produced marked increases in c-myc mRNA levels within 3 hr. Recombinant interleukin 2 (rIL-2; Cetus) had little effect on c-myc expression but, in combination with PHA, it augmented levels of c-myc transcripts measured at 24 hr but not at 3 hr. Adding various inhibitors of lymphocyte proliferation to PHA-stimulated cultures revealed that cyclosporin A, dexamethasone, and OKT11A antibody (anti-sheep erythrocyte receptor) diminished levels of c-myc mRNA measured at 3 hr and 24 hr, whereas anti-Tac (anti-IL-2-receptor) inhibited at 24 hr but not at 3 hr. Thus, cyclosporin A, dexamethasone, and OKT11A interfere with early events of T-cell activation, whereas anti-Tac acts later. Hydroxyurea and 42/6 antibody (anti-transferrin receptor), which impair the G1----S transition in cycling cells, failed to inhibit c-myc expression and instead delayed the decrease in c-myc mRNA levels that normally occurs with the onset of DNA synthesis. These data indicate that c-myc is regulated (in normal lymphocytes) at several points in the cell cycle.