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

被引:164
作者
Shattuck-Brandt, RL
Varilek, GW
Radhika, A
Yang, FJ
Washington, MK
DuBois, RN
机构
[1] Vanderbilt Univ, Dept Med, Div Gastroenterol, Sch Med, Nashville, TN 37232 USA
[2] Vanderbilt Univ, Dept Cell Biol, Sch Med, Nashville, TN 37232 USA
[3] Vanderbilt Univ, Sch Med, Dept Pathol, Nashville, TN 37232 USA
[4] Univ Kentucky, Coll Med, Dept Internal Med, Markey Canc Ctr, Lexington, KY USA
[5] Univ Kentucky, Coll Med, Grad Program Nutr Sci, Lexington, KY USA
关键词
D O I
10.1016/S0016-5085(00)70216-2
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
Background & 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 cu-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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页码:337 / 345
页数:9
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