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Temporal and quantitative regulation of mitogen-activated protein kinase (MAPK) modulates cell motility and invasion

Oncogene volume 20, pages 4209–4218 (2001)Cite this article

Abstract

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, TGFα stimulation induced only transient MAPK activation, leading to a transient increase in cell migration. However, MDA 231 and MDA 468 cells, TGFα stimulation induced sustained MAPK activation, which correlated with enhanced cell motility and in vitro invasion. Serum stimulation activates ERK/MAPK activity persistently in 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 non-invasive MCF-7 breast cancer cells.

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Acknowledgements

This work was supported in part by NIH Grant CA 64248 (to KB Reddy) and CA 83964 (to KB Reddy).

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  1. Department of Pathology, Wayne State University School of Medicine, Detroit, 48201, Michigan, MI, USA

    Joseph S Krueger, Venkateshwar G Keshamouni, Natasha Atanaskova & Kaladhar B Reddy

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  1. Joseph S Krueger
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  2. Venkateshwar G Keshamouni
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  3. Natasha Atanaskova
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  4. Kaladhar B Reddy
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Krueger, J., Keshamouni, V., Atanaskova, N. et al. Temporal and quantitative regulation of mitogen-activated protein kinase (MAPK) modulates cell motility and invasion. Oncogene 20, 4209–4218 (2001). https://doi.org/10.1038/sj.onc.1204541

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