Lack of inducible nitric oxide synthase promotes intestinal tumorigenesis in the ApcMin/+ mouse
Gastroenterology, 2001•Elsevier
Background & Aims: The role of the inducible isoform of nitric oxide synthase (Nos2 or iNOS)
in intestinal tumorigenesis is unclear. Conflicting data also exist regarding the ability of Nos2
to modulate expression and/or activity of cyclooxygenase 2 (Cox-2), which promotes
intestinal tumorigenesis. Therefore, we determined the effect of a null Nos2 genotype on
intestinal tumorigenesis and Cox-2 expression/activity in the ApcMin/+ mouse model of
familial adenomatous polyposis. Methods: ApcMin/+ Nos2−/− mice were generated by …
in intestinal tumorigenesis is unclear. Conflicting data also exist regarding the ability of Nos2
to modulate expression and/or activity of cyclooxygenase 2 (Cox-2), which promotes
intestinal tumorigenesis. Therefore, we determined the effect of a null Nos2 genotype on
intestinal tumorigenesis and Cox-2 expression/activity in the ApcMin/+ mouse model of
familial adenomatous polyposis. Methods: ApcMin/+ Nos2−/− mice were generated by …
Background & Aims
The role of the inducible isoform of nitric oxide synthase (Nos2 or iNOS) in intestinal tumorigenesis is unclear. Conflicting data also exist regarding the ability of Nos2 to modulate expression and/or activity of cyclooxygenase 2 (Cox-2), which promotes intestinal tumorigenesis. Therefore, we determined the effect of a null Nos2 genotype on intestinal tumorigenesis and Cox-2 expression/activity in the ApcMin/+ mouse model of familial adenomatous polyposis.
Methods
ApcMin/+Nos2−/− mice were generated by successive crosses between C57BL/6-ApcMin/+ and C57BL/6-Nos2tm1Lau mice. Adenoma characteristics of age-matched ApcMin/+Nos2+/+ and ApcMin/+Nos2−/− mice were compared. The level and cellular localization of Nos2 messenger RNA (mRNA) expression in ApcMin/+Nos2+/+ mouse intestine was determined. Cox-2 expression and activity were measured in both intestinal tissue and bone marrow-derived macrophages in vitro.
Results
ApcMin/+Nos2−/− mice developed significantly more intestinal adenomas than ApcMin/+Nos2+/+ littermates. Epithelial cell Nos2 mRNA expression was decreased in adenomas compared with histologically normal ApcMin/+Nos2+/+ intestine. There was no significant difference in Cox-2 expression or activity in either intestine or bone marrow—derived macrophages from ApcMin/+Nos2+/+ and ApcMin/+Nos2−/− animals.
Conclusions
Nos2 plays an antineoplastic role in the ApcMin/+ mouse model of familial adenomatous polyposis. Nos2 does not modulate Cox-2 expression or activity in the ApcMin/+ mouse.
Elsevier
