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 Hellmich

doi:10.1007/s10620-007-0122-9

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 Hellmich

Research output: Contribution to journal › Article › peer-review

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 p38^MAPK-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)
Pages (from-to)	2045-2052
Number of pages	8
Journal	Digestive Diseases and Sciences
Volume	53
Issue number	8
DOIs	https://doi.org/10.1007/s10620-007-0122-9
State	Published - Aug 2008
Externally published	Yes

Keywords

Bombesin
Cyclooxygenase-2
Gastrointestinal cancer
TGF-β

ASJC Scopus subject areas

Physiology
Gastroenterology

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10.1007/s10620-007-0122-9

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@article{db356e51579b47429451b84230efc4ad,

title = "Synergistic regulation of COX-2 expression by bombesin and transforming growth factor-β",

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.",

keywords = "Bombesin, Cyclooxygenase-2, Gastrointestinal cancer, TGF-β",

author = "Guo, {Yan Shi} and Zihong Chen and Wen, {Xiao Dong} and Ko, {Tien C.} and Townsend, {Courtney M.} and Mark Hellmich",

note = "Funding Information: 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.",

year = "2008",

month = aug,

doi = "10.1007/s10620-007-0122-9",

language = "English (US)",

volume = "53",

pages = "2045--2052",

journal = "Digestive Diseases and Sciences",

issn = "0163-2116",

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T1 - Synergistic regulation of COX-2 expression by bombesin and transforming growth factor-β

AU - Guo, Yan Shi

AU - Chen, Zihong

AU - Wen, Xiao Dong

AU - Ko, Tien C.

AU - Townsend, Courtney M.

AU - Hellmich, Mark

N1 - Funding Information: 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.

PY - 2008/8

Y1 - 2008/8

N2 - 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.

AB - 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.

KW - Bombesin

KW - Cyclooxygenase-2

KW - Gastrointestinal cancer

KW - TGF-β

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

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