Epidermal growth factor regulates PAI-1 expression via activation of the transcription factor Elk-1.
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.
Wyrzykowska
Paulina
P
Department of Cell Biochemistry, Jagiellonian University, Poland.
Stalińska
Krystyna
K
Wawro
Mateusz
M
Kochan
Jakub
J
Kasza
Aneta
A
D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D001665:Binding Sites / Q000187:drug effects; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D004815:Epidermal Growth Factor / Q000494:pharmacology / Q000502:physiology*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D010766:Phosphorylation / Q000187:drug effects; D017395:Plasminogen Activator Inhibitor 1 / Q000235:genetics* / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000187:drug effects; D011485:Protein Binding / Q000187:drug effects; D011494:Protein Kinases / Q000378:metabolism; D050784:Proto-Oncogene Protein c-ets-1 / Q000378:metabolism; D015533:Transcriptional Activation / Q000187:drug effects; D014162:Transfection; D014407:Tumor Cells, Cultured; D050807:ets-Domain Protein Elk-1 / Q000378:metabolism* / Q000502:physiology
D017395:Plasminogen Activator Inhibitor 1; D050784:Proto-Oncogene Protein c-ets-1; D050807:ets-Domain Protein Elk-1; D004815:Epidermal Growth Factor; D011494:Protein Kinases