Interactive effects of nitric oxide and the p53 tumor suppressor gene in carcinogenesis and tumor progression

S Ambs, SP Hussain, CC Harris - The FASEB Journal, 1997 - Wiley Online Library
S Ambs, SP Hussain, CC Harris
The FASEB Journal, 1997Wiley Online Library
The tumor suppressor gene product p53 plays an important role in the cellular response to
DNA damage. DNA damage can lead to p53‐mediated growth arrest and apoptosis. High
concentrations of nitric oxide (NO) and NO metabolites such as peroxynitrite and NO2 cause
DNA damage and have been shown to be mutagenic. Furthermore, NO induces p53
accumulation and, as part of a feedback loop, p53 mediates transcriptional transrepression
of inducible nitric oxide synthase. Recent studies have shown increased expression and …
The tumor suppressor gene product p53 plays an important role in the cellular response to DNA damage. DNA damage can lead to p53‐mediated growth arrest and apoptosis. High concentrations of nitric oxide (NO) and NO metabolites such as peroxynitrite and NO2 cause DNA damage and have been shown to be mutagenic. Furthermore, NO induces p53 accumulation and, as part of a feedback loop, p53 mediates transcriptional transrepression of inducible nitric oxide synthase. Recent studies have shown increased expression and activity of nitric oxide synthase isoforms in human cancer. NO has both genotoxic and angiogenic properties, so that increased NO production may select mutant p53 cells and contribute to human carcinogenesis and tumor progression.—Ambs, S., Hussain, S. P., Harris, C. C. Interactive effects of nitric oxide and the p53 tumor suppressor gene in carcinogenesis and tumor progression. FASEB J. 11, 443–448 (1997)
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