| PTPase inhibition restores ERK1/2 phosphorylation and protects mammary epithelial cells from apoptosis. | |
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MedLine Citation:
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PMID: 16176809 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Specific survival signals derived from extracellular matrix (ECM) and growth factors are required for mammary epithelial cell survival. We have previously demonstrated that inhibition of ECM-induced ERK1/2 MAPK pathway with PD98059 leads to apoptosis in primary mouse mammary epithelial cells. In this study, we have further investigated MAPK signal transduction in cell survival of these cells cultured on a laminin rich reconstituted basement membrane. ERK1/2 phosphorylation is activated in the absence of insulin by cell-cell substratum interactions that cause ligand-independent EGFR transactivation. Intact EGFR signal transduction is required for ECM determined cell survival as the EGFR pathway inhibitor, AG1478, induces apoptosis of these cultures. Rescue of AG1478 or PD98059 treated cultures by PTPase inhibition with vanadate restores cellular phospho-ERK1/2 levels and prevents apoptosis. These results emphasize that ERK1/2 phosphorylation and inhibition of PTPase activity are necessary for PMMEC cell survival. |
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Authors:
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Fiona Furlong; Darren Finlay; Finian Martin |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Biochemical and biophysical research communications Volume: 336 ISSN: 0006-291X ISO Abbreviation: Biochem. Biophys. Res. Commun. Publication Date: 2005 Nov |
Date Detail:
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Created Date: 2005-10-03 Completed Date: 2005-12-12 Revised Date: 2013-06-03 |
Medline Journal Info:
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Nlm Unique ID: 0372516 Medline TA: Biochem Biophys Res Commun Country: United States |
Other Details:
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Languages: eng Pagination: 1292-9 Citation Subset: IM |
Affiliation:
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UCD School of Biomolecular and Biomedical Science, Conway Institute, University College Dublin, Belfield, Ireland. fiona.furlong@ucd.ie |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Apoptosis / physiology* Cell Adhesion Cell Survival Cells, Cultured Epithelial Cells / metabolism, physiology* Female Flavonoids / pharmacology Insulin / physiology Laminin / metabolism Mammary Glands, Animal / cytology* Mice Mitogen-Activated Protein Kinase 1 / metabolism* Mitogen-Activated Protein Kinase 3 / metabolism* Phosphorylation Protein Kinase Inhibitors / pharmacology Protein Tyrosine Phosphatases / antagonists & inhibitors, metabolism* Quinazolines Receptor, Epidermal Growth Factor / metabolism Tyrphostins / pharmacology Vanadates / pharmacology |
| Chemical | |
Reg. No./Substance:
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0/2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one; 0/Flavonoids; 0/Insulin; 0/Laminin; 0/Protein Kinase Inhibitors; 0/Quinazolines; 0/Tyrphostins; 0/Vanadates; 170449-18-0/tyrphostin AG 1478; EC 2.7.10.1/Receptor, Epidermal Growth Factor; EC 2.7.11.24/Mitogen-Activated Protein Kinase 1; EC 2.7.11.24/Mitogen-Activated Protein Kinase 3; EC 3.1.3.48/Protein Tyrosine Phosphatases |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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