Association with nitric oxide synthase expression, p53 alteration and TGF β signal-transduction abnormality in human tumors

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Nitric oxide (NO) is free radical gas which is associated with several events in cell biology, including angiogenesis, neural transmission and cytotoxicity. Frequent iNOS expressions have been observed in many types of carcinomas. Immunoreactivity of iNOS has also suggested that iNOS might play an important role in the behavior of tumors. We immunohistochemically examined the expression of iNOS in patients with urothelial cancer, esophageal cancer, lung cancer and renal cancer to determine the significance for the tumor behavior. No urothelial cancers exhibited negative iNOS immunostaining were found. Of 105 tumors, fifty-five esophageal cancers were positive with anti-iNOS antibody. Positive immunoreaction of iNOS was also found more than 80% of lung cancers. No significant association between iNOS immunoreactivity and any clinicopathological factors as well as p53 immunoreactivity were found in each human cancer examined.It is accepted that mutation of the p53 gene plays a critical r … More ole in the process of the carcinogenesis of human cancer. Small numbers of in vivo studies have revealed that there was strong positive relationship between p53 gene mutation and the presence of iNOS in human malinancy, suggesting that an excess of endogenously formed NO directly generates a p53 gene mutation. We present here that there was significant relationship between p53 alterations not in urothelial cancers but in esophageal cancers.Genomic DNA from the RCC patients was examined by VHL gene analysis to characterize the genotype of alterations and their frequency of involvement in iNOS or p53 expression. Of 17 RCCs with VLH mutations, fifteen tumors (88.3%) exhibited cytoplasmic immunostaining, including five homogenous and ten heterogeneous. Of 9 RCCs without VHL mutations, four tumors (44.4%) exhibited cytoplasmic immunostaining, including two homogenous and two heterogeneous. No association between p53 overexpression and iNOS immunoreactivity or VHL alteration in RCCs examined were found. These findings provide evidence for frequent iNOS protein expression in RCCs with VHL mutations. Less