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

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

Research output: Contribution to journalArticle

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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 - 1999
Externally publishedYes

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Plasminogen Activators
Urokinase-Type Plasminogen Activator
Transforming Growth Factors
Cyclooxygenase 2
Carcinogenesis
Urokinase Plasminogen Activator Receptors
Antibodies
Cyclooxygenase 2 Inhibitors
Plasminogen Activator Inhibitor 1
Collagen Type I
Colon
Complementary DNA
Western Blotting
Enzyme-Linked Immunosorbent Assay
Cell Line
1-((4-methylsulfonyl)phenyl)-3-trifluoromethyl-5-(4-fluorophenyl)pyrazole
Neoplasms

ASJC Scopus subject areas

  • Surgery

Cite this

O'Mahony, C. A., Beauchamp, R. D., Albo, D., Tsujii, M., Sheng, H. M., Shao, J., ... 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

Cyclooxygenase-2 alters transforming growth factor-β1 response during intestinal tumorigenesis. / O'Mahony, C. A.; Beauchamp, R. D.; Albo, D.; Tsujii, M.; Sheng, H. M.; Shao, J.; Dubois, R. N.; Berger, David H.

In: Surgery, Vol. 126, No. 2, 1999, p. 364-370.

Research output: Contribution to journalArticle

O'Mahony, CA, Beauchamp, RD, Albo, D, Tsujii, M, Sheng, HM, Shao, J, Dubois, RN & Berger, DH 1999, 'Cyclooxygenase-2 alters transforming growth factor-β1 response during intestinal tumorigenesis', Surgery, vol. 126, no. 2, pp. 364-370. https://doi.org/10.1016/S0039-6060(99)70178-9
O'Mahony, C. A. ; Beauchamp, R. D. ; Albo, D. ; Tsujii, M. ; Sheng, H. M. ; Shao, J. ; Dubois, R. N. ; Berger, David H. / Cyclooxygenase-2 alters transforming growth factor-β1 response during intestinal tumorigenesis. In: Surgery. 1999 ; Vol. 126, No. 2. pp. 364-370.
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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.",
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AU - O'Mahony, C. A.

AU - Beauchamp, R. D.

AU - Albo, D.

AU - Tsujii, M.

AU - Sheng, H. M.

AU - Shao, J.

AU - Dubois, R. N.

AU - Berger, David H.

PY - 1999

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N2 - 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.

AB - 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.

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