TY - JOUR
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 R.
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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U2 - 10.1007/s10620-007-0122-9
DO - 10.1007/s10620-007-0122-9
M3 - Article
C2 - 18095163
AN - SCOPUS:46449100403
SN - 0163-2116
VL - 53
SP - 2045
EP - 2052
JO - Digestive Diseases and Sciences
JF - Digestive Diseases and Sciences
IS - 8
ER -