Inducible nitric oxide synthase expression of tumor and stromal cells is associated with the progression of 7,12-dimethylbenz[a]anthracene-induced rat mammary tumors

The purpose of this study was to investigate the alteration of inducible nitric oxide synthase (iNOS) expression in rodent mammary tumors. We examined iNOS expression by immunohistochemistry and Western blot analysis in 7,12-dimethylbenz[a]anthracene (DMBA)-induced rat mammary tumors. In Western blot analysis, invasive carcinomas showed strong expression of iNOS; however, carcinomas in situ, atypical tumors and normal mammary tissue revealed insignificant expression. In immunohistochemistry, tumors revealed positive immunoreactivity in either tumor epithelial, stromal or endothelial cells. In particular, invasive carcinomas showed strong expression at the tumor cells bordering on glandular lumen containing necrotic or apoptotic nuclear debris. Invasive carcinomas showed higher positive immunoreactivity of iNOS compared with normal mammary tissue, atypical tumors, and carcinomas in situ. Stromal iNOS expression was correlated with apoptotic count. These results suggest that iNOS expression of tumor and stromal cells is associated with the progression of DMBA-induced rat mammary tumors.