Synergistic regulation of COX-2 expression by bombesin and transforming growth factor-β

Yan Shi Guo, Zihong Chen, Xiao Dong Wen, Tien C. Ko, Courtney M. Townsend, Mark R. Hellmich

Research output: Contribution to journalArticle

4 Scopus citations

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 languageEnglish (US)
Pages (from-to)2045-2052
Number of pages8
JournalDigestive Diseases and Sciences
Volume53
Issue number8
DOIs
StatePublished - Aug 1 2008

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Keywords

  • Bombesin
  • Cyclooxygenase-2
  • Gastrointestinal cancer
  • TGF-β

ASJC Scopus subject areas

  • Physiology
  • Gastroenterology

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