Aspirin promotes TFF2 gene activation in human gastric cancer cell lines.
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.
Azarschab
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P
Division of Molecular Genetics, Institute of Anthropology and Human Genetics, University of Tübingen, Wilhelmstr. 27, D-72074, Tübingen, Germany.
Al-Azzeh
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E
Kornberger
W
W
Gött
P
P
D016718:Arachidonic Acid / Q000378:metabolism / Q000494:pharmacology; D001241:Aspirin / Q000494:pharmacology*; D005770:Gastrointestinal Neoplasms / Q000235:genetics* / Q000378:metabolism; D017930:Genes, Reporter / Q000235:genetics; D006133:Growth Substances / Q000235:genetics*; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology; D008954:Models, Biological; D009077:Mucins; D009124:Muscle Proteins; D009479:Neuropeptides; D010455:Peptides / Q000235:genetics*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020218:Response Elements / Q000235:genetics; D017384:Sequence Deletion / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects; D019311:Staurosporine / Q000494:pharmacology; D015533:Transcriptional Activation / Q000187:drug effects*; D014162:Transfection; D000071164:Trefoil Factor-2; D000071165:Trefoil Factor-3; D014407:Tumor Cells, Cultured
D006133:Growth Substances; D009077:Mucins; D009124:Muscle Proteins; D009479:Neuropeptides; D010455:Peptides; D012333:RNA, Messenger; C000604007:TFF2 protein, human; C099037:TFF3 protein, rat; C000604008:Tff2 protein, rat; D000071164:Trefoil Factor-2; D000071165:Trefoil Factor-3; D016718:Arachidonic Acid; D011493:Protein Kinase C; D019311:Staurosporine; D001241:Aspirin; D007213:Indomethacin