DNA hypermethylation at the pS2 promoter region is associated with early stage of stomach carcinogenesis

pS2, a member of the trefoil peptide family, has been suggested to be a gas tric-specific tumor suppressor. We examined the expression of pS2 in gastri c carcinomas, adenomas and non-neoplastic mucosa and analyzed the DNA methy lation in the pS2 promoter. Reduced expression of pS2 was frequently associ ated with well-differentiated adenocarcinomas. The CpG sites within the pro moter region of the pS2 gene were methylated in pS2-negative gastric carcin oma cell Lines whereas it was not in pS2-positive cell line. The promoter m ethylation was detected in gastric carcinoma tissues and intestinal metapla sia with reduced pS2 expression whereas none of the carcinomas with preserv ed pS2 expression showed the promoter methylation. These findings suggest t hat reduced expression of pS2 due to the promoter methylation may participa te in an early stage of stomach carcinogenesis, especially of well differen tiated type. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved.