Cyclooxygenase 2 expression is increased in the stroma of colon carcinomas from IL-10(-/-) mice

Rebecca L. Shattuck-Brandt, Gary W. Varilek, Aramandla Radhika, Fajun Yang, M. Kay Washington, Raymond N. DuBois

Research output: Contribution to journalArticle

158 Citations (Scopus)

Abstract

Background and Aims: The pathological and molecular changes associated with colitis-associated colorectal cancer and sporadic colorectal cancer are considered to be distinct. Therefore, we have used a mouse model of ulcerative colitis to determine if expression of the enzyme cyclooxygenase (COX)-2 is increased in colitis-associated tumors. Methods: Reverse- transcription polymerase chain reaction and Western analysis were used to determine if COX-2 expression is increased in these tumors; in situ hybridization and immunohistochemistry were used to determine the localization of COX-2. Results: Increased levels of COX-2 messenger RNA and protein were detected in interleukin (IL)-10 (-/-) tumors and in an inflamed region of the colon that contained no macroscopically detected tumors. This expression was localized to the inflammatory cells associated with ulcerated regions of the tumor by in situ hybridization and immunohistochemistry. Increased COX-2 expression was also associated with the areas of the tumor expressing α-smooth muscle actin, which is a molecular marker for subepithelial myofibroblasts. The association between COX-2 expression and subepithelial myofibroblasts was also noted in tumors derived from the multiple intestinal neoplasia mice (Min/+) and from carcinogen-induced tumors. Conclusions: These results indicate that COX-2 is expressed very early in the pathogenesis of colitis-associated tumors, and that the expression pattern is similar to that seen in tumors from azoxymethane- treated and Min/+ mice.

Original languageEnglish (US)
Pages (from-to)337-345
Number of pages9
JournalGastroenterology
Volume118
Issue number2
StatePublished - 2000
Externally publishedYes

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Cyclooxygenase 2
Interleukin-10
Colon
Carcinoma
Neoplasms
Colitis
Myofibroblasts
In Situ Hybridization
Colorectal Neoplasms
Immunohistochemistry
Azoxymethane
Smooth Muscle Tumor
Ulcerative Colitis
Carcinogens
Reverse Transcription
Actins
Polymerase Chain Reaction
Messenger RNA
Enzymes

ASJC Scopus subject areas

  • Gastroenterology

Cite this

Shattuck-Brandt, R. L., Varilek, G. W., Radhika, A., Yang, F., Washington, M. K., & DuBois, R. N. (2000). Cyclooxygenase 2 expression is increased in the stroma of colon carcinomas from IL-10(-/-) mice. Gastroenterology, 118(2), 337-345.

Cyclooxygenase 2 expression is increased in the stroma of colon carcinomas from IL-10(-/-) mice. / Shattuck-Brandt, Rebecca L.; Varilek, Gary W.; Radhika, Aramandla; Yang, Fajun; Washington, M. Kay; DuBois, Raymond N.

In: Gastroenterology, Vol. 118, No. 2, 2000, p. 337-345.

Research output: Contribution to journalArticle

Shattuck-Brandt, RL, Varilek, GW, Radhika, A, Yang, F, Washington, MK & DuBois, RN 2000, 'Cyclooxygenase 2 expression is increased in the stroma of colon carcinomas from IL-10(-/-) mice', Gastroenterology, vol. 118, no. 2, pp. 337-345.
Shattuck-Brandt RL, Varilek GW, Radhika A, Yang F, Washington MK, DuBois RN. Cyclooxygenase 2 expression is increased in the stroma of colon carcinomas from IL-10(-/-) mice. Gastroenterology. 2000;118(2):337-345.
Shattuck-Brandt, Rebecca L. ; Varilek, Gary W. ; Radhika, Aramandla ; Yang, Fajun ; Washington, M. Kay ; DuBois, Raymond N. / Cyclooxygenase 2 expression is increased in the stroma of colon carcinomas from IL-10(-/-) mice. In: Gastroenterology. 2000 ; Vol. 118, No. 2. pp. 337-345.
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AU - Yang, Fajun

AU - Washington, M. Kay

AU - DuBois, Raymond N.

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AB - Background and Aims: The pathological and molecular changes associated with colitis-associated colorectal cancer and sporadic colorectal cancer are considered to be distinct. Therefore, we have used a mouse model of ulcerative colitis to determine if expression of the enzyme cyclooxygenase (COX)-2 is increased in colitis-associated tumors. Methods: Reverse- transcription polymerase chain reaction and Western analysis were used to determine if COX-2 expression is increased in these tumors; in situ hybridization and immunohistochemistry were used to determine the localization of COX-2. Results: Increased levels of COX-2 messenger RNA and protein were detected in interleukin (IL)-10 (-/-) tumors and in an inflamed region of the colon that contained no macroscopically detected tumors. This expression was localized to the inflammatory cells associated with ulcerated regions of the tumor by in situ hybridization and immunohistochemistry. Increased COX-2 expression was also associated with the areas of the tumor expressing α-smooth muscle actin, which is a molecular marker for subepithelial myofibroblasts. The association between COX-2 expression and subepithelial myofibroblasts was also noted in tumors derived from the multiple intestinal neoplasia mice (Min/+) and from carcinogen-induced tumors. Conclusions: These results indicate that COX-2 is expressed very early in the pathogenesis of colitis-associated tumors, and that the expression pattern is similar to that seen in tumors from azoxymethane- treated and Min/+ mice.

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