Trefoil factor family (TFF) peptides promote cell migration, heal the mucosa and may suppress tumor growth, In reporter gene assays we show that aspirin (1-12 mM) evokes a six-fold up-regulation of TFF2, but not TFF1 and TFF3 transcription in human gastrointestinal cell lines, 6 h after application up-regulation of endogenous TFF2 mRNA was observed. TFF2 transcription was enhanced by indomethacin and arachidonic acid but repressed by staurosporine, suggesting mediation via protein kinase C, We mapped an aspirin responding element -536 to -758 by upstream of TFF2, Upregulation of TFF2 by aspirin may partially explain the chemopreventive potential of low dose aspirin in gastrointestinal carcinogenesis. (C) 2001 Federation of European Biochemical Societies, Published by Elsevier Science B.V. All rights reserved.