Regulation of gene expression by tumor promoters. II. Control of cell shape and developmental programs for macrophages and granulocytes in human myeloid leukemic cells
Regulation of gene expression by tumor promoters. II. Control of cell shape and developmental programs for macrophages and granulocytes in human myeloid leukemic cells
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肿瘤启动子对基因表达的调节。
DOI：
10.1002/ijc.2910280306
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发表时间：
1981
影响因子：
6.4
通讯作者：
L. Sachs
中科院分区：
文献类型：
--
作者：
D. Liebermann;B. Hoffman‐Liebermann;L. Sachs
在人髓性白血病细胞系（HL 60）中，使用细胞质蛋白变化的二维凝胶图谱分析了巨噬细胞和粒细胞发育程序的调节，该细胞系可被巨噬细胞和粒细胞诱导（MGI）蛋白和肿瘤促进剂12-O-十四烷酰基-佛波醇-13-乙酸酯（TPA）诱导分化为巨噬细胞，并被二甲基亚砜（DMSO）诱导分化为粒细胞。对不同诱导剂诱导的蛋白质变化的研究表明，MGI或TPA诱导的巨噬细胞分化具有类似的发育程序，其不同于DMSO诱导的粒细胞程序。与来自人外周血的正常细胞的比较表明，在HL 60细胞中诱导的发育程序与这两种细胞类型的正常分化程序相关。与MGI和DMSO不同，TPA诱导HL 60细胞快速附着于培养皿表面。TPA和DMSO联合处理显示细胞贴壁、广泛铺展、特异性蛋白调节和巨噬细胞程序表达。将TPA添加到由DMSO诱导的粒细胞程序的细胞中导致细胞附着和铺展以及从粒细胞到巨噬细胞程序的迁移。结果表明，悬浮液中的细胞可以根据诱导剂表达巨噬细胞或粒细胞程序，并且与TPA诱导的细胞附着相关的细胞形状变化可以调节特定蛋白质并将发育程序限制为巨噬细胞。有人建议，在体内环境中的细胞有关的可能性，细胞粘附，这可以调节肿瘤促进剂，可能发挥重要作用，在确定髓系和其他类型的细胞的发育程序。
Regulation of the developmental programs for macrophages and granulocytes has been analysed, using two‐dimensional gel electrophorels of the cytoplasmic protein changes, in a human myeloid leukemic cell line (HL60) that can be induced to differentiate to macrophages by the macrophage and granulocyte‐inducing (MGI) protein and the tumor promoter 12‐O‐tetradecanoyl‐phorbol‐13‐acetate (TPA), and to granulocytes by dimethylsulfoxide (DMSO). Studies on the protein changes induced by the different inducers showed a similar developmental program for macrophage differentiation induced by MGI or TPA, which differed from the beginning from the granulocyte program induced by DMSO. Comparison with normal cells from human peripheral blood has shown that the developmental programs induced in the HL60 cells are relevant to the normal programs of differentiation for these two cell types. Unlike MGI and DMSO, TPA induces rapid attachment of the HL60 cells to the surface of the Petri dish. Combined treatment with TPA and DMSO showed cell attachment, extensive spreading of the cells, the regulation of specific proteins and expression of the macrophage program. The addition of TPA to cells induced for the granulocyte program by DMSO resulted in cell attachment and spreading and a switchover from the granulocyte to the macrophage program. The results indicate that cells in suspension can express either the macrophage or granulocyte program depending on the inducer, and that changes in cell shape associated with cell attachment induced by TPA can regulate specific proteins and restrict the developmental program to macrophages. It is suggested that the in vivo environment of cells in relation to the possibilities for cell adhesion, which can be regulated by tumor promotors, may play a major role in determining the developmental program of myeloid and other cell types.