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

doi:10.1074/jbc.m110.121830

Cited by 47 publications

(60 citation statements)

References 70 publications

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“…For flow cytometry analysis, soft agar colony-growth and cell proliferation/viability MTT analysis, cells were processed 24 -72 h post-transfection. Whole cell protein extracts were prepared by cell lysis and immunoblot as indicated (40).…”

Section: Methodsmentioning

confidence: 99%

“…Cell Culture, RNA Interference, Cell Lysis, and ImmunoblotAll parental human breast cancer cell line were obtained from ATTC, and were grown as indicated (40). LNCaP prostate adenocarcinoma cell lines was grown in Roswell Park Memorial Institute medium (RPMI) 1640 (Invitrogen) supplemented with 10% FBS, 2 mM L-glutamine, 100 units/ml penicillin and 100 g/ml streptomycin.…”

Section: Methodsmentioning

confidence: 99%

“…Gene Expression Profiling by DNA Microarray and Semiquantitative and Quantitative Real-time PCR-DNA microarray analysis of gene expression was performed using total RNA from MCF-7 cells treated or not with PMA for 4 days, as previously described (40). Semi-quantitative RT-PCR or quantitative real-time PCR (qPCR) were performed using total RNA from cell lines treated or not with PMA, FGF, or serum (FBS) for different times.…”

Section: Methodsmentioning

confidence: 99%

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Epidermal Growth Factor Receptor (EGFR)-mediated Positive Feedback of Protein-tyrosine Phosphatase ϵ (PTPϵ) on ERK1/2 and AKT Protein Pathways Is Required for Survival of Human Breast Cancer Cells

Nunes‐Xavier

Elson

Pulido

2012

Journal of Biological Chemistry

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Background:To investigate the functional role of PTP⑀ in human breast cancer cell lines. Results: PTP⑀ was up-regulated in human breast cancer cells in an EGFR-and ERK1/2-dependent manner. PTP⑀ displayed a positive role in survival of human breast cancer cells. Conclusion: PTP⑀ generates a positive feedback regulatory loop required for survival of human breast cancer cells. Significance: PTP⑀ could be a putative target in breast cancer treatment.Increased tyrosine phosphorylation has been correlated with human cancer, including breast cancer. In general, the activation of tyrosine kinases (TKs) can be antagonized by the action of protein-tyrosine phosphatases (PTPs). However, in some cases PTPs can potentiate the activation of TKs. In this study, we have investigated the functional role of PTP⑀ in human breast cancer cell lines. We found the up-regulation and activation of receptor PTP⑀ (RPTP⑀) in MCF-7 cells and MDA-MB-231 upon PMA, FGF, and serum stimulation, which depended on EGFR and ERK1/2 activity. Diminishing the expression of PTP⑀ in human breast cancer cells abolished ERK1/2 and AKT activation, and decreased the viability and anchorage-independent growth of the cells. Conversely, stable MCF-7 cell lines expressing inducible high levels of ectopic PTP⑀ displayed higher activation of ERK1/2 and anchorage-independent growth. Our results demonstrate that expression of PTP⑀ is up-regulated and activated in breast cancer cell lines, through EGFR, by sustained activation of the ERK1/2 pathway, generating a positive feedback regulatory loop required for survival of human breast cancer cells.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Epidermal Growth Factor Receptor (EGFR)-mediated Positive Feedback of Protein-tyrosine Phosphatase ϵ (PTPϵ) on ERK1/2 and AKT Protein Pathways Is Required for Survival of Human Breast Cancer Cells

Nunes‐Xavier

Elson

Pulido

2012

Journal of Biological Chemistry

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“…It is widely accepted that SCFAs inhibit cell proliferation and at higher concentrations induce apoptosis in various cancer cells [36][37][38][39][40][41] whereas, the effect of PMA on cell survival and proliferation appears to be more diverse; it depends on the contributing PKC isoform, the activity of interacting signaling pathways and the duration of treatment [21,[42][43][44][45][46]. Here we examined the proliferation rate of cells during a prolonged treatment (4 days) with SCFAs or PMA.…”

Section: Effects Of Scfas and Pma On Cellular Proliferation And Diffementioning

confidence: 99%

Histone deacetylase inhibitor- and PMA-induced upregulation of PMCA4b enhances Ca2+ clearance from MCF-7 breast cancer cells

et al. 2014

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The expression of the plasma membrane Ca 2+ ATPase (PMCA) isoforms is altered in several types of cancer cells suggesting that they are involved in cancer progression. In this study we induced differentiation of MCF-7 breast cancer cells by histone deacetylase inhibitors (HDACis) such as short chain fatty acids (SCFAs) or suberoylanilide hydroxamic acid (SAHA), and by phorbol 12-myristate 13-acetate (PMA) and found strong upregulation of PMCA4b protein expression in response to these treatments. Furthermore, combination of HDACis with PMA augmented cell differentiation and further enhanced PMCA4b expression both at mRNA and protein levels. Immunocytochemical analysis revealed that the upregulated protein was located mostly in the plasma membrane. To examine the functional consequences of elevated PMCA4b expression, the characteristics of intracellular Ca 2+ signals were investigated before and after differentiation inducing treatments, and also in cells overexpressing PMCA4b. The increased PMCA4b expression -either by treatment or overexpression -led to enhanced Ca 2+ clearance from the stimulated cells. We found pronounced PMCA4 protein expression in normal breast tissue samples highlighting the importance of this pump for the maintenance of mammary epithelial Ca 2+ homeostasis. These results suggest that modulation of Ca 2+ signaling by enhanced PMCA4b expression may contribute to normal development of breast epithelium and may be lost in cancer.3

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“…Upregulation of DUSP3 and DUSP5 has been reported in PMA-treated MCF-7 and BKBR3 breast cancer cell lines. Activation of the ERK1/2 pathway and accelerated growth arrest of BC cells, has been observed following silencing of either DUSP3 or DUSP5, and overexpression of either phosphatase prevents growth inhibition and cell migration (242).…”

Section: Breast Cancermentioning

confidence: 99%

The regulatory roles of phosphatases in cancer

et al. 2013

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The relevance of potentially reversible post-translational modifications required for controlling cellular processes in cancer is one of the most thriving arenas of cellular and molecular biology. Any alteration in the balanced equilibrium between kinases and phosphatases may result in development and progression of various diseases, including different types of cancer, though phosphatases are relatively under-studied. Loss of phosphatases such as PTEN (phosphatase and tensin homologue deleted on chromosome 10), a known tumour suppressor, across tumour types lends credence to the development of phosphatidylinositol 3 - kinase inhibitors alongside the use of phosphatase expression as a biomarker, though phase 3 trial data are lacking. In this review, we give an updated report on phosphatase dysregulation linked to organ-specific malignancies. © 2014 American Heart Association, Inc

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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

Cited by 47 publications

References 70 publications

Epidermal Growth Factor Receptor (EGFR)-mediated Positive Feedback of Protein-tyrosine Phosphatase ϵ (PTPϵ) on ERK1/2 and AKT Protein Pathways Is Required for Survival of Human Breast Cancer Cells

Epidermal Growth Factor Receptor (EGFR)-mediated Positive Feedback of Protein-tyrosine Phosphatase ϵ (PTPϵ) on ERK1/2 and AKT Protein Pathways Is Required for Survival of Human Breast Cancer Cells

Histone deacetylase inhibitor- and PMA-induced upregulation of PMCA4b enhances Ca2+ clearance from MCF-7 breast cancer cells

The regulatory roles of phosphatases in cancer

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