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.

Research highlights
► EGF activates ERK.
► Activation of transcription factor Elk-1.
► Regulation of human PAI-1 expression via the sequence TTCCTG (CAGGAA on the complementary strand) located between −42 and −36bp. Elk-1 is bound directly to this sequence in the absence of SRF.