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Ape-1\/ref-1 (Apex-1) is a multifunctional protein that promotes DNA binding of redox-sensitive transcription factors, such as AP-1, and repairs oxidative DNA damage. A validated mouse endothelial cell (EOMA) tumor model was used to demonstrate that Nox-4-derived H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub> causes DNA oxidation that induces Apex-1 expression. Apex-1 functions as a chaperone to keep transcription factors in a reduced state. In EOMA cells Apex-1 enables AP-1 binding to the monocyte chemoattractant protein-1 ( mcp-1) promoter and expression of that protein is required for endothelial cell tumor formation. Intraperitoneal injection of the small molecule inhibitor E3330, which specifically targets Apex-1 redox-sensitive functions, resulted in a 50% decrease in tumor volume compared with mice injected with vehicle control ( n = 6 per group), indicating that endothelial cell tumor proliferation is dependent on Apex-1 expression. These are the first reported results to establish Nox-4 induction of Apex-1 as a mechanism promoting endothelial cell tumor formation. <\/jats:p>","DOI":"10.1152\/ajpcell.00022.2015","type":"journal-article","created":{"date-parts":[[2015,6,25]],"date-time":"2015-06-25T02:41:39Z","timestamp":1435200099000},"page":"C296-C307","source":"Crossref","is-referenced-by-count":15,"title":["Endothelial cell tumor growth is Ape\/ref-1 dependent"],"prefix":"10.1152","volume":"309","author":[{"given":"Ayan","family":"Biswas","sequence":"first","affiliation":[{"name":"Department of Plastic Surgery, The Ohio State University Wexner Medical Center, Columbus, Ohio;"},{"name":"Davis Heart and Lung Research Institute, The Ohio State University Wexner Medical Center, Columbus, Ohio; and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Savita","family":"Khanna","sequence":"additional","affiliation":[{"name":"Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, 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