Nitric Oxide Synthase Activity in Human Thyroid Papillary Carcinomas

抄録

In human thyroid carcinoma, there is no evidence that the activity of NO synthase and the contribution of endothelial NOS (eNOS) have been determined. To determine the relationship between NOS and human thyroid carcinomas, we assayed eNOS expression and assessed the activity of NOS in thyroid papillary carcinomas (TPC), benign thyroid tumors, and normal thyroid tissues. We investigated the involvement of NO in TPC using an assay system to measure NOS activity by high performance liquid chromatography (HPLC), which could be applied to determine citrulline enrichment. The TPC showed high levels of NOS activity. Moreover, histochemical staining with NADPH-diaphorase revealed a positive reaction in the TPC samples, localized to the blood vessel endothelium. These cells were much less stained, however, in normal thyroid tissue. When we incubated these samples with an anti-eNOS antibody, we observed staining of the TPC samples, again localized to the blood vessel endothelium cells, but much less than in the normal thyroid samples. RT-PCR amplification using eNOS specific primers revealed that eNOS mRNA was abundant in the TPC samples, but was much less expressed in normal thyroid. These results show that NOS activity exists in TPC and that it is associated with malignancy.