p53 and vascular endothelial growth factor regulate tumor growth of NOS2-expressing human carcinoma cells

Stefan Ambs*, William G. Merriam, Mofolusara O. Ogunfusika, William P. Bennett, Naoko Ishibe, S. Perwez Hussain, Edith E. Tzeng, David A. Geller, Timothy R. Billiar, Curtis C. Harris

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

262 Scopus citations

Abstract

The finding of frequent nitric oxide synthase expression in human cancers indicates that nitric oxide has a pathophysiological role in carcinogenesis. To determine the role of nitric oxide in tumor progression, we generated human carcinoma cell lines that produced nitric oxide constitutively. Cancer cells expressing inducible nitric oxide synthase that had wild-type p53 had reduced tumor growth in athymic nude mice, whereas those with mutated p53 had accelerated tumor growth associated with increased vascular endothelial growth factor expression and neovascularization. Our data indicate that tumor-associated nitric oxide production may promote cancer progression by providing a selective growth advantage to tumor cells with mutant p53, and that inhibitors of inducible nitric oxide synthase may have therapeutic activity in these tumors.

Original languageEnglish
Pages (from-to)1371-1376
Number of pages6
JournalNature Medicine
Volume4
Issue number12
DOIs
StatePublished - Dec 1998
Externally publishedYes

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