Abstract
Overexpression of cyclooxygenase-2 (COX-2), an inducible enzyme regulating prostaglandin release, is mechanistically linked to the development, growth, and spread of gastrointestinal (GI) cancers. GI peptide bombesin (BBS) was reported to stimulate COX-2 gene expression. Here we show that TGF-β1 dramatically enhances the BBS-induced expression of COX-2 mRNA and protein, and the release of PGE2 in the model rat intestinal epithelial cell (RIE-1) line. The synergistic increase in COX-2 levels results from a combination of enhanced COX-2 transcription and reduced mRNA degradation. BBS, but not TGF-β1, stimulated COX-2 promoter activity, and TGF-β1 enhanced COX-2 mRNA stability through a p38MAPK-dependent pathway. The synergistic regulation of COX-2 expression by TGF-β1 and BBS may contribute to the upregulation of COX-2 in GI cancers.
Original language | English (US) |
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Pages (from-to) | 2045-2052 |
Number of pages | 8 |
Journal | Digestive Diseases and Sciences |
Volume | 53 |
Issue number | 8 |
DOIs | |
State | Published - Aug 2008 |
Keywords
- Bombesin
- Cyclooxygenase-2
- Gastrointestinal cancer
- TGF-β
ASJC Scopus subject areas
- Physiology
- Gastroenterology