Nitric oxide synthase and p53 expression in human gastric cancer

Abstract

Nitric oxide is a messenger molecule involved in many physiological functions and patophysiological actions. This highly reactive short-lived molecule can cause DNA damage and activate subsequent lethal reactions including energy depletion and cell necrosis. The tumor suppressor gene product p53 plays an important role in the cellular response to DNA damage. The present study investigates the expression and distribution of isozymes of nitric oxide synthase (NOS) in association with p53 expression and apoptosis in gastric cancer and normal gastric mucosa. Using immunohistochemistry, we stained and scored resected gastric tumors and non involved gastric mucosa from 20 patients with gastric adenocarcinomas. In tumor tissue we observed significant reduction of NOS isoforms expression but apoptosis, wild-type and mutant form of p53 was detectable in all tumors, especially in intestinal type of gastric cancer. In non tumor involved gastric mucosa the localization of NOS was predominantly in deeper mucosal layer, whereas apoptosis was detectable in superficial mucosal layer. Mutant form of p53 was not detected in normal gastric mucosa, only in mucosa which shown intestinal metaplasia. Our results show that loss of NOS exopression is associated with overexpression of wild type and mutant form of p53. The corresponding apoptosis in tumor cells is not associated with NO production as had been predicted.