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Differential Up-regulation of MAP Kinase Phosphatases MKP3/DUSP6 and DUSP5 by Ets2 and c-Jun Converge in the Control of the Growth Arrest Versus Proliferation Response of MCF-7 Breast Cancer Cells to Phorbol Ester

Nunes-Xavier, Caroline E. ; Tárrega, Céline ; Cejudo-Marín, Rocío ; Frijhoff, Jeroen ; Sandin, Åsa ; Östman, Arne ; Pulido, Rafael

The Journal of biological chemistry, 2010-08, Vol.285 (34), p.26417-26430 [Periódico revisado por pares]

United States: Elsevier Inc

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Título:
Differential Up-regulation of MAP Kinase Phosphatases MKP3/DUSP6 and DUSP5 by Ets2 and c-Jun Converge in the Control of the Growth Arrest Versus Proliferation Response of MCF-7 Breast Cancer Cells to Phorbol Ester
Autor: Nunes-Xavier, Caroline E. ; Tárrega, Céline ; Cejudo-Marín, Rocío ; Frijhoff, Jeroen ; Sandin, Åsa ; Östman, Arne ; Pulido, Rafael
Assuntos: Breast Cancer ; Breast Neoplasms - pathology ; Cell Line, Tumor ; Cell Proliferation ; Dual Specificity Phosphatase 6 - genetics ; Dual-Specificity Phosphatases - genetics ; Female ; Humans ; MAP Kinases (MAPKs) ; Medicin och hälsovetenskap ; Molecular Bases of Disease ; Phorbol Esters ; Phorbol Esters - pharmacology ; Phosphatase ; Phosphoprotein Phosphatase ; Proto-Oncogene Protein c-ets-2 - physiology ; Proto-Oncogene Proteins c-jun - physiology ; Signal Transduction ; Up-Regulation - genetics
É parte de: The Journal of biological chemistry, 2010-08, Vol.285 (34), p.26417-26430
Notas: Both authors were supported by the European Union Marie Curie Research Training Programme.
Descrição: Different levels of regulation account for the inactivation of MAP kinases by MAPK phosphatases (MKPs), in a cell type- and stimuli-dependent manner. MCF-7 human breast carcinoma cells treated with the phorbol 12-myristate 13-acetate (PMA) suffer growth arrest and show morphological alterations, which depend on the activation of the ERK1/2 MAP kinases. MKP3/DUSP6 and DUSP5 MAP kinase phosphatases, two negative regulators of ERK1/2, were specifically up-regulated in MCF-7 and SKBR3 cells in response to PMA. MKP3 and DUSP5 up-regulation required the prolonged activation of the ERK1/2 pathway, and correlated with the shutdown of this route. MKP3 induction relied on the activation of the Ets2 transcription factor, whereas DUSP5 induction depended on the activation of c-Jun. Diminishing the expression of MKP3 and DUSP5 raised the activation of ERK1/2, and accelerated growth arrest of PMA-treated MCF-7 cells. Conversely, MCF-7 cell lines expressing high levels of MKP3 or DUSP5 did not undergo PMA-triggered growth arrest, displayed a migratory phenotype, and formed colonies in soft agar. We propose that the differential up-regulation of MKP3 by Ets2 and of DUSP5 by c-Jun may converge in similar functional roles for these MAP kinase phosphatases in the growth arrest versus proliferation decisions of breast cancer cells.
Editor: United States: Elsevier Inc
Idioma: Inglês

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Differential Up-regulation of MAP Kinase Phosphatases MKP3/DUSP6 and DUSP5 by Ets2 and c-Jun Converge in the Control of the Growth Arrest Versus Proliferation Response of MCF-7 Breast Cancer Cells to Phorbol Ester

Nunes-Xavier, Caroline E. ; Tárrega, Céline ; Cejudo-Marín, Rocío ; Frijhoff, Jeroen ; Sandin, Åsa ; Östman, Arne ; Pulido, Rafael

United States: Elsevier Inc

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