Our data show that Cox-2 is expressed in gastric adenomas of the TFF1 −/− mice and suggest that inhibition of Cox-2 disturbs the integrity of the adenoma by promoting ulceration and inflammation. All untreated TFF1 −/− mice had an adenoma ( n = 7), but none demonstrated the combination of ulceration and inflammation.
This effect of the drug was adenoma specific, because no histological alterations were observed in the non-neoplastic gastric or intestinal tissues in the TFF1 −/− or wild-type mice receiving the drug treatment. for 3 months) caused ulceration and inflammation of the adenoma in all treated TFF1 −/− mice ( n = 7).
Nonneoplastic gastrointestinal tissues of wild-type or TFF1 −/− mice expressed low or nondetectable levels of Cox-2. Cox-2 mRNA and protein were strongly expressed in the pyloric adenomas of the TFF1 −/− mice as detected by in situ hybridization and immunohistochemistry. Because inhibition of Cox-2 suppresses tumor growth in several animal models, we studied expression of Cox-2 and effect of a selective Cox-2 inhibitor celecoxib in gastrointestinal tissues of the TFF1-deficient mice. Mice deficient for trefoil factor 1 (TFF1) develop a pyloric adenoma with full penetrance. Expression of cyclooxygenase-2 (Cox-2) is elevated in gastric adenocarcinomas and precursor lesions leading to this disease.
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