Acetylation of core
histones is closely linked to transcriptional activation of various genes. The acetylation levels of nucleosomal
histones can be modified through a balance of
histone acetyltransferases and deacetylases. To elucidate the role of
histone acetylation in human gastric
carcinogenesis, we studied the status of
histone H4 acetylation in gastric
carcinoma tissues and corresponding non-neoplastic mucosa. The status of
histone acetylation was assessed by examining the expression of acetylated
histone H4 through Western blotting and immunohistochemistry using an anti-acetylated
histone H4 antibody. The levels of acetylated
histone H4 expression were obviously reduced in 72% (13/18) of gastric
carcinomas in comparison with non-neoplastic mucosa by Western blotting. In immunohistochemistry, acetylated
histone H4 was clearly detected in the nuclei of both non-neoplastic epithelial and stromal cells, whereas the levels of acetylated
histone H4 were heterogeneous or reduced in 66% (38/57) of gastric
carcinomas and 46% (6/13) of gastric
adenomas. Reduced expression of acetylated
histone H4 was also observed in some areas of intestinal
metaplasia adjacent to
carcinomas. Reduction in the expression of acetylated
histone H4 was significantly correlated with advanced stage, depth of
tumor invasion and
lymph node metastasis. These results suggest that low levels of
histone acetylation may be closely associated with the development and progression of gastric
carcinomas, possibly through alteration of gene expression.