Temporal and quantitative regulation of mitogen-activated protein kinase (MAPK) modulates cell motility and invasion
Temporal and quantitative regulation of mitogen-activated protein kinase (MAPK) modulates cell motility and invasion
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DOI：
10.1038/sj.onc.1204541
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发表时间：
2001-07-12
期刊：
影响因子：
8
通讯作者：
Reddy, KB
中科院分区：
文献类型：
--
作者：
Krueger, JS;Keshamouni, VG;Reddy, KB
我们发现，ER阴性的侵袭性人乳腺癌细胞株MDA-MB-468和MDA-MB-231比ER阳性的非侵袭性人乳腺癌细胞MCF-7具有更高的有丝分裂原激活蛋白激酶(ERK1&2/MAPK)。在MCF-7细胞中，转化生长因子α刺激只能诱导一过性的MAPK激活，导致细胞迁移的一过性增加。然而，对MDA231和MDA468细胞，TCFα刺激诱导持续的MAPK激活，这与细胞的运动性增强和体外侵袭有关，血清刺激激活ERK/MAPK活性持续激怒ER阳性和ER阴性的乳腺癌细胞，导致细胞迁移增强和持续。在MDA-MB-468细胞中，反义MEK表达抑制MAPK激活，可显著抑制细胞迁移和体外侵袭。相反，表达结构性激活的MEK的MCF-7细胞表现出明显的MAPK活性和细胞迁移增加，但这并不能增强体外侵袭。MAPK激活和抑制的动力学曲线表明，在ER阳性和ER阴性的人乳腺癌细胞中，MAPK激活的持续时间和幅度与细胞迁移之间存在关系。这些研究表明，细胞的运动受到MAPK激活的幅度和持续时间的调节；但MAPK的激活增加可能不足以允许非侵袭性MCF-7乳腺癌细胞的体外侵袭。
We have shown that ER-negative and invasive human breast cancer cell lines MDA-MB-468 and MDA-MB-231 have constitutively higher mitogen activated protein kinase (ERK1&2/MAPK) when compared to the ER-positive and non-invasive MCF-7 human breast cancer cells. In MCF-7 cells, TGF alpha stimulation induced only transient MAPK activation, leading to a transient increase in cell migration. However, MDA 231 and MDA 468 cells, TCF alpha stimulation induced sustained MAPK activation, which correlated with enhanced cell motility and in vitro invasion, Serum stimulation activates ERK/MAPK activity persistently ire both ER-positive and ER-negative breast cancer cells, leading to enhanced and sustained cell migration. Inhibition of MAPK activation by anti-sense MEK expression in MDA-MB-468 cells significantly inhibits cell migration and in vitro invasion. In contrast, MCF-7 cells expressing constitutively activated MEK show a significant increase in MAPK activity and cell migration, but this failed to enhance in vitro invasion. The kinetic profiles of MAPK activation and inhibition show a relationship between the duration and magnitude of MAPK activation and cell migration in both ER-positive and ER-negative human breast cancer cells. These studies show that cell motility is modulated by the magnitude and the duration of MAPK activation; but increased activation of MAPK may not be sufficient to allow in vitro invasion in noninvasive MCF-7 breast cancer cells.