Myeloid leukemia cell growth and differentiation are independent of mitogen-activated protein kinase ERK1/2 activation
Myeloid leukemia cell growth and differentiation are independent of mitogen-activated protein kinase ERK1/2 activation
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DOI：
10.1074/jbc.275.10.7189
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发表时间：
2000-03-10
影响因子：
4.8
通讯作者：
Crespo, P
中科院分区：
文献类型：
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作者：
Ajenjo, N;Aaronson, DS;Crespo, P
丝裂原活化蛋白激酶ERK 1/2途径在大多数细胞系统中控制细胞增殖和分化是必不可少的。因此，它被认为是一个潜在的目标，为癌症治疗。为此，我们研究了ERK激活在髓系白血病细胞生长和分化中的作用。使用一组有代表性的髓性白血病细胞系，我们表明，细胞增殖并不伴随着增加ERK 1/2激活，和促有丝分裂刺激并没有增强ERK活性。此外，通过抑制剂PD 98059或显性抑制突变体ERK 2消除ERK功能对增殖没有显著影响。在各种分化诱导剂的帮助下，我们发现在同一细胞系中，分化为给定的谱系可以在有或没有ERK 1/2激活的情况下发生，这取决于刺激。此外，分化剂在存在或不存在ERK刺激的情况下可以具有相同的效果，这取决于细胞系。ERK抑制不影响分化引起的刺激，其影响伴随着ERK激活。最后，组成性ERK活性对增殖和分化也是无效的。因此，我们的研究结果表明，ERK 1/2激活不是白血病细胞生长和分化的必要条件。
The mitogen-activated protein kinase ERK1/2 pathway is essential in the control of cell proliferation and differentiation in most cellular systems. As such, it has been considered a potential target for antineoplastic therapy. For this purpose, we have examined the role of ERK activation in myeloid leukemia cell growth and differentiation. Using a representative set of myeloid leukemia cell lines, we show that cell proliferation was not accompanied by increases on ERK1/2 activation, and mitogenic stimulation did not enhance ERK activity. Moreover, abolition of ERK function by the inhibitor PD98059 or by a dominant inhibitory mutant ERK2 had no significant effects on proliferation. With the aid of various differentiation inducers, we found that within the same cell line, differentiation to a given lineage could occur with and without ERK1/2 activation, depending on the stimulus. Also, a differentiator could have the same effect in the presence or absence of ERK stimulation, depending on the cell line. ERK inhibition did not affect the differentiation elicited by stimuli whose effects were accompanied by ERK activation. Finally, constitutive ERK activity was also ineffective on proliferation and differentiation. Thus, our results indicate that ERK1/2 activation is not an essential requirement for leukemic cell growth and differentiation.