INHIBITION OF TPA-INDUCED MONOCYTIC DIFFERENTIATION IN THP-1 HUMAN MONOCYTIC LEUKEMIC-CELLS BY STAUROSPORINE, A POTENT PROTEIN KINASE-C INHIBITOR
INHIBITION OF TPA-INDUCED MONOCYTIC DIFFERENTIATION IN THP-1 HUMAN MONOCYTIC LEUKEMIC-CELLS BY STAUROSPORINE, A POTENT PROTEIN KINASE-C INHIBITOR
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DOI：
10.1016/0145-2126(90)90034-7
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发表时间：
1990-01-01
影响因子：
2.7
通讯作者：
CHEN, B
中科院分区：
文献类型：
--
作者：
BARENDSEN, N;MUELLER, M;CHEN, B
THP-1是一种不依赖因子的单核细胞白血病细胞系，经12- o -四癸烯基磷酸-13-乙酸（TPA）治疗后分化为贴壁巨噬细胞。与正常细胞不同，THP-1细胞仅显示极低水平的原癌基因c-FMS RNA，其编码M-CSF膜受体。Northern blot分析显示，在tpa诱导的单核细胞分化过程中，THP-1细胞中c-FMS mRNA水平显著升高。尽管TPA处理后获得了功能活性并诱导了c-fms转录本，但在THP-1细胞上未检测到表面M-CSF受体。当用staurosporine（一种有效的蛋白激酶C （PK-C）抑制剂）预处理THP-1细胞时，与TPA相关的诱导活性完全消失。由此得出结论，PK-C系统的激活是THP-1细胞单核细胞分化起始所必需的代谢级联反应的一部分。
THP-1 is a factor-independent, monocytic leukemia cell line which differentiates into adherent macrophages upon treatment with 12-O-tetra-decanoylphorbol-13-acetate (TPA). Unlike its normal counterparts, THP-1 cells display only minimal levels of proto-oncogene c-FMS RNA which encode for membrane M-CSF receptors. Northern blot analysis showed that the c-FMS mRNA levels in THP-1 cells was greatly ehanced during TPA-induced monocytic differentiation. Despite the acquisition of functional activities and induction of c-fms transcripts after TPA treatment, no surface M-CSF receptors were detected on the THP-1 cells. The inducing activity associated with TPA was completely abrogated when THP-1 cells were pretreated with staurosporine, a potent protein kinase C (PK-C) inhibitor. It is concluded that the activation of the PK-C system is a part of the metabolic cascade essential for the initiation of monocytic differentiation in THP-1 cells.