Cyclooxygenase-2 alters transforming growth factor-β1 response during intestinal tumorigenesis

C. A. O'Mahony, R. D. Beauchamp, Daniel Albo, M. Tsujii, H. M. Sheng, J. Shao, R. N. Dubois, David H. Berger

Research output: Contribution to journalArticle

24 Scopus citations

Abstract

Background: Recent investigation suggests that cyclooxygenase-2 plays an important role in colorectal carcinogenesis. Transforming growth factor- betal (TGF-β1) is one of the most potent stimulators of cyclooxygenase-2 expression. A key step in intestinal tumorigenesis involves alteration of the normal cellular response to TGF-β1. We have hypothesized that overexpression of cyclooxygenase-2 alters intestinal epithelial response to TGF-β1. Methods: RIE-1 cells were stably transfected with rat cyclooxygenase-2 complementary DNA in either the sense (RIE-S) or antisense (RIE-AS) orientation. Tumor cell invasion was assessed with a modified Boyden collagen type I invasion assay in the presence of TGF-β1, antibody to urokinase plasminogen activator (uPA), or the selective cyclooxygenase-2 inhibitor SC- 58125. Expression of uPA, uPA receptor, and plasminogen activator inhibitor- 1 were determined by Western blot and enzyme-linked immunosorbent assay. Results: RIE-1 and RIE-AS did not invade although RIE-S cells were minimally invasive at baseline. TGF-β1 had no effect on RIE-1 or RIE-AS invasion; however, TGF-β1 significantly upregulated RIE-S cell invasion. All 3 RIE cell lines produce minimal uPA under basal conditions. TGF-β1 upregulated uPA production only in the RIE-S cells. Both antibody to uPA and SC-58125 reversed TGF-β-mediated RIE-S cell invasion. SC-58125 inhibited TGF-β- mediated RIE-S uPA production. Conclusions: These results demonstrate that overexpression of cyclooxygenase-2 alters intestinal epithelial response to TGF-β1, which may be a mechanism by which cyclooxygenase-2 promotes colon carcinogenesis.

Original languageEnglish (US)
Pages (from-to)364-370
Number of pages7
JournalSurgery
Volume126
Issue number2
DOIs
StatePublished - Jan 1 1999
Externally publishedYes

ASJC Scopus subject areas

  • Surgery

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    O'Mahony, C. A., Beauchamp, R. D., Albo, D., Tsujii, M., Sheng, H. M., Shao, J., Dubois, R. N., & Berger, D. H. (1999). Cyclooxygenase-2 alters transforming growth factor-β1 response during intestinal tumorigenesis. Surgery, 126(2), 364-370. https://doi.org/10.1016/S0039-6060(99)70178-9