Abstract
PAI-1 (plasminogen activator inhibitor-1) in breast cancer cells is involved in tumour development and metastasis of breast cancer cells. PAI-1 function and the regulation of its expression have been precisely investigated. Here we report that EGF, which promotes breast cancer tumour growth and survival, rapidly induces PAI-1 expression in the breast adenocarcinoma cell line MCF-7 through the activation of the transcription factor Elk-1. We have found that the PAI-1 promoter fragment (-140 to +173) containing the Ets consensus binding site is activated by Elk-1. Chromatin immunoprecipitation analysis confirms in vivo binding of Elk-1 to the PAI-1 promoter and demonstrates that Elk-1 phosphorylation on the Ets binding site is EGF-dependent.
Copyright © 2010 Elsevier B.V. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adenocarcinoma / genetics
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Adenocarcinoma / metabolism
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Adenocarcinoma / pathology
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Binding Sites / drug effects
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Breast Neoplasms / genetics
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Breast Neoplasms / metabolism
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Breast Neoplasms / pathology
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Epidermal Growth Factor / pharmacology
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Epidermal Growth Factor / physiology*
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Female
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Gene Expression Regulation, Neoplastic / drug effects
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Humans
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Phosphorylation / drug effects
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Plasminogen Activator Inhibitor 1 / genetics*
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Plasminogen Activator Inhibitor 1 / metabolism
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Promoter Regions, Genetic / drug effects
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Protein Binding / drug effects
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Protein Kinases / metabolism
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Proto-Oncogene Protein c-ets-1 / metabolism
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Transcriptional Activation / drug effects
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Transfection
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Tumor Cells, Cultured
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ets-Domain Protein Elk-1 / metabolism*
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ets-Domain Protein Elk-1 / physiology
Substances
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Plasminogen Activator Inhibitor 1
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Proto-Oncogene Protein c-ets-1
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ets-Domain Protein Elk-1
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Epidermal Growth Factor
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Protein Kinases