Document Detail

PTPase inhibition restores ERK1/2 phosphorylation and protects mammary epithelial cells from apoptosis.
MedLine Citation:
PMID:  16176809     Owner:  NLM     Status:  MEDLINE    
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.
Fiona Furlong; Darren Finlay; Finian Martin
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Biochemical and biophysical research communications     Volume:  336     ISSN:  0006-291X     ISO Abbreviation:  Biochem. Biophys. Res. Commun.     Publication Date:  2005 Nov 
Date Detail:
Created Date:  2005-10-03     Completed Date:  2005-12-12     Revised Date:  2013-06-03    
Medline Journal Info:
Nlm Unique ID:  0372516     Medline TA:  Biochem Biophys Res Commun     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1292-9     Citation Subset:  IM    
UCD School of Biomolecular and Biomedical Science, Conway Institute, University College Dublin, Belfield, Ireland.
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MeSH Terms
Apoptosis / physiology*
Cell Adhesion
Cell Survival
Cells, Cultured
Epithelial Cells / metabolism,  physiology*
Flavonoids / pharmacology
Insulin / physiology
Laminin / metabolism
Mammary Glands, Animal / cytology*
Mitogen-Activated Protein Kinase 1 / metabolism*
Mitogen-Activated Protein Kinase 3 / metabolism*
Protein Kinase Inhibitors / pharmacology
Protein Tyrosine Phosphatases / antagonists & inhibitors,  metabolism*
Receptor, Epidermal Growth Factor / metabolism
Tyrphostins / pharmacology
Vanadates / pharmacology
Reg. No./Substance:
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, Epidermal Growth Factor; EC Protein Kinase 1; EC Protein Kinase 3; EC Tyrosine Phosphatases

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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