P53 and vascular endothelial growth factor regulate tumor growth of NOS2-expressing human carcinoma cells

The finding of frequent nitric oxide synthase expression in human cancers i ndicates that nitric oxide has a pathophysiological role in carcinogenesis. To determine the role of nitric oxide in tumor progression, we generated h uman carcinoma cell lines that produced nitric oxide constitutively. Cancer cells expressing inducible nitric oxide synthase that had wild-type p53 ha d reduced tumor growth in athymic nude mice, whereas those with mutated p53 had accelerated tumor growth associated with increased vascular endothelia l growth factor expression and neovascularization. Our data indicate that t umor-associated nitric oxide production may promote cancer progression by p roviding a selective growth advantage to tumor cells with mutant p53, and t hat inhibitors of inducible nitric oxide synthase may have therapeutic acti vity in these tumors.