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Synergistic Regulation of COX-2 Expression by Bombesin and Transforming Growth Factor-β

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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.

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Acknowledgments

This work was supported by National Institutes of Health Grants PO1 DK35608, RO1 DK48345, and R01 DK58119. The authors thank Dr. Harvey R. Herschman for providing COX-2 promoter constructs and COX-2 cDNA probe. We also thank Eileen Figueroa, Steve Schuenke, and Karen Martin for the preparation of this manuscript.

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Authors and Affiliations

  1. Department of Surgery, The University of Texas Medical Branch, 301 University Boulevard, Galveston, TX, 77555-0722, USA

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

  2. Sealy Center for Cancer Cell Biology, The University of Texas Medical Branch, Galveston, TX, USA

    Tien C. Ko & Mark R. Hellmich

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  1. Yan-Shi Guo
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  2. Zihong Chen
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  3. Xiao-Dong Wen
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Correspondence to Yan-Shi Guo.

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Guo, YS., Chen, Z., Wen, XD. et al. Synergistic Regulation of COX-2 Expression by Bombesin and Transforming Growth Factor-β. Dig Dis Sci 53, 2045–2052 (2008). https://doi.org/10.1007/s10620-007-0122-9

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  • DOI: https://doi.org/10.1007/s10620-007-0122-9

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