Namciu S, Lieberman M A, Stavnezer E
Department of Moleuclar Genetics, Biochemistry, and Microbiology, University of Cincinnati College of Medicine, Ohio 45267-0524.
Oncogene. 1994 May;9(5):1407-16.
Overexpression of v-ski blocks the terminal differentiation of chicken erythroblasts, and in cooperation with v-sea causes transformation of these cells, indicating that c-ski may play a role in regulating either proliferation or differentiation in hematopoietic cells. We examined c-ski expression in four different myeloid cell lines which can be induced to differentiate by exposure to phorbol 12-myristate 13-acetate (PMA). Two of the cell lines are multipotent and have the ability to differentiate into either erythrocytes or megakaryocytes (K562 and HEL cells), one cell line differentiates exclusively into megakaryocytes (CHRF-288-11), and the fourth cell line differentiates into either monocytes or granulocytes (HL-60). Our findings indicate that c-ski mRNA is up regulated by PMA only in those cell lines which respond by differentiating along the megakaryocyte lineage. The extent of differentiation and the observed increase in c-ski mRNA levels are positively correlated with the PMA concentration used to induce differentiation. Experiments in which CHRF-288-11 cells were treated with the protein kinase C (PKC) activator bryostatin 1 indicate that c-ski mRNA induction is not a general effect of PKC activation. The results strongly suggest that c-ski expression is correlated with megakaryocyte maturation.
v-ski的过表达会阻断鸡红细胞的终末分化，并且与v-sea协同作用会导致这些细胞发生转化，这表明c-ski可能在调节造血细胞的增殖或分化中发挥作用。我们检测了四种不同的髓系细胞系中c-ski的表达，这些细胞系可通过暴露于佛波醇12-肉豆蔻酸酯13-乙酸酯（PMA）诱导分化。其中两个细胞系具有多能性，能够分化为红细胞或巨核细胞（K562和HEL细胞），一个细胞系仅分化为巨核细胞（CHRF-288-11），第四个细胞系分化为单核细胞或粒细胞（HL-60）。我们的研究结果表明，仅在那些通过沿巨核细胞谱系分化做出反应的细胞系中，PMA会上调c-ski mRNA的表达。分化程度以及观察到的c-ski mRNA水平的增加与用于诱导分化的PMA浓度呈正相关。用蛋白激酶C（PKC）激活剂苔藓抑素1处理CHRF-288-11细胞的实验表明，c-ski mRNA的诱导不是PKC激活的普遍效应。结果强烈表明c-ski的表达与巨核细胞成熟相关。
