Epidermal growth factor regulates PAI-1 expression via activation of the transcription factor Elk-1.

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.

• Authors: Paulina Wyrzykowska, Krystyna Stalińska, Mateusz Wawro, Jakub Kochan, Aneta Kasza
• Journal: Biochimica et biophysica acta (Biochim Biophys Acta) Vol. 1799 Issue 9 Pg. 616-21 (Sep 2010) ISSN: 0006-3002 [Print] Netherlands
• PMID: 20727996 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2010 Elsevier B.V. All rights reserved.

Chemical References

• Plasminogen Activator Inhibitor 1
• Proto-Oncogene Protein c-ets-1
• ets-Domain Protein Elk-1
• Epidermal Growth Factor
• Protein Kinases

Topics

• Adenocarcinoma (genetics, metabolism, pathology)
• Binding Sites (drug effects)
• Breast Neoplasms (genetics, metabolism, pathology)
• Epidermal Growth Factor (pharmacology, physiology)
• Female
• Gene Expression Regulation, Neoplastic (drug effects)
• Humans
• Phosphorylation (drug effects)
• Plasminogen Activator Inhibitor 1 (genetics, metabolism)
• Promoter Regions, Genetic (drug effects)
• Protein Binding (drug effects)
• Protein Kinases (metabolism)
• Proto-Oncogene Protein c-ets-1 (metabolism)
• Transcriptional Activation (drug effects)
• Transfection
• Tumor Cells, Cultured
• ets-Domain Protein Elk-1 (metabolism, physiology)