TGFβ1 诱导 THP-1 细胞分化为巨噬细胞时原癌基因表达的变化

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对重组转化生长因子β1(TGF-β1)诱导前单核白血病细胞系THP-1细胞向巨噬细胞分化过程中核内原癌基因表达的动态变化进行了研究。结果发现,在诱导分化过程中不同的原癌基因表达变化不仅具有时序性,调节方式也呈多样性。c-fos、c-junmRNA表达变化在时间上有一致性,诱导分化早期(24小时)贴壁细胞的表达量明显增加,延长rhTGP-β1作用时间至48~72小时时,这种上调作用消失,回复到对照组THP-1细胞原有的或低于原有的表达水平。c-myc在细胞分化过程中表达逐渐降低,作用72小时时表达量不足对照组细胞的10%。而c-sis在rhTGP-β1作用72小时内未发现其表达被调节。提示c-fos、c-jun基因在分化早期的表达上调,以及c-myc基因在分化中期的表达被强烈抑制可能分别在分化进程中发挥重要作用。 The dynamic changes of protooncogene expression in the nuclear macrophage during the differentiation of THP-1 cells, a pre-mononuclear leukemia cell line, induced by recombinant transforming growth factor β1 (TGF-β1) were studied. It was found that the expression of different proto-oncogenes during the differentiation process was not only time-sequential, but also varied in the mode of regulation. The changes of c-fos and c-jun mRNA expression were consistent in time, and the expression level of adherent cells was significantly increased in the early stage of differentiation (24 hours). When the time of rhTGP-β1 was increased to 48 to 72 hours, this up-regulation disappeared. , return to the control group THP-1 cells original or lower than the original expression level. The expression of c-myc gradually decreased during cell differentiation, and the expression level was less than 10% of cells in the control group at 72 hours. However, the expression of c-sis was not regulated in rhTGP-β1 within 72 hours. It suggests that the up-regulation of c-fos and c-jun genes in early differentiation and the strong inhibition of c-myc gene expression in the mid-differentiation period may play an important role in the differentiation process.
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