Cyclooxygenase 2 expression is increased in the stroma of colon carcinomas from IL-10(-/-) mice.
OBJECTIVE
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 alpha-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.
Shattuck-Brandt
R L
RL
Department of Cell Biology, Vanderbilt School of Medicine, Nashville, Tennessee 37232-2279, USA.
Varilek
G W
GW
Radhika
A
A
Yang
F
F
Washington
M K
MK
DuBois
R N
RN
D000818:Animals; D001397:Azoxymethane; D003106:Colon / Q000201:enzymology* / Q000473:pathology; D003110:Colonic Neoplasms / Q000139:chemically induced / Q000201:enzymology* / Q000473:pathology*; D051546:Cyclooxygenase 2; D017403:In Situ Hybridization; D007249:Inflammation; D016753:Interleukin-10 / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D007413:Intestinal Mucosa / Q000201:enzymology* / Q000473:pathology; D007527:Isoenzymes / Q000032:analysis / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009130:Muscle, Smooth / Q000201:enzymology / Q000473:pathology; D011451:Prostaglandin-Endoperoxide Synthases / Q000032:analysis / Q000235:genetics*; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017154:Stromal Cells / Q000201:enzymology / Q000473:pathology
D007527:Isoenzymes; D012333:RNA, Messenger; D016753:Interleukin-10; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; D001397:Azoxymethane