Aspirin promotes TFF2 gene activation in human gastric cancer cell lines

• Published in: FEBS letters Vol. 488; no. 3; pp. 206 - 210
• Main Authors: Azarschab, Pia, Al-Azzeh, Ezzal-din, Kornberger, Wolfgang, Gött, Peter
• Format: Journal Article
• Language: English
• Published: England Elsevier B.V 19.01.2001
• Subjects: Arachidonic Acid - metabolism; Arachidonic Acid - pharmacology; Aspirin; Aspirin - pharmacology; Carcinogenesis; Gastrointestinal Neoplasms - genetics; Gastrointestinal Neoplasms - metabolism; Genes, Reporter - genetics; Growth Substances - genetics; Humans; Indomethacin - pharmacology; Models, Biological; Mucins; Muscle Proteins; Neuropeptides; Peptides - genetics; Protein Kinase C - antagonists & inhibitors; Response Elements - genetics; RNA, Messenger - genetics; RNA, Messenger - metabolism; Sequence Deletion - genetics; Signal transduction; Signal Transduction - drug effects; Spasmolytic polypeptide; Staurosporine - pharmacology; Transcriptional Activation - drug effects; Transcriptional regulation; Transfection; Trefoil Factor-2; Trefoil Factor-3; Trefoil peptide; Tumor Cells, Cultured; Signal transduction; Trefoil peptide; Aspirin; Transcriptional regulation; Carcinogenesis; Spasmolytic polypeptide
• ISSN: 0014-5793; 1873-3468
• DOI: 10.1016/S0014-5793(00)02422-4

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 −546 to −758 bp upstream of TFF2. Up-regulation of TFF2 by aspirin may partially explain the chemopreventive potential of low dose aspirin in gastrointestinal carcinogenesis.