trypsinogen and Esophageal-Neoplasms

Trypsin is a serine protease family member with a potential role in cancer invasion. We investigated trypsinogen expression at the RNA level in 49 esophageal squamous cell carcinomas (ESCCs) and 72 gastric adenocarcinomas. Almost all primary ESCC tissues (95%) showed reduced expression, and 9 of 13 ESCC cell lines were silenced for trypsinogen expression. Absent expression correlated with promoter hypermethylation of trypsinogen-4 by bisulfite DNA sequence. Moreover, we detected promoter hypermethylation in 50% of primary ESCCs by methylation-specific PCR. A subset of gastric adenocarcinomas (71%) also showed reduced trypsinogen accompanied by reduction in PAR2, a G protein activated by trypsin, and a propensity to penetrate beyond the gastric wall (P = 0.001). Our results support the notion that trypsin plays a tumor-suppressive role in human carcinoma.

Topics: Adenocarcinoma; Base Sequence; Carcinoma, Squamous Cell; Disease Progression; DNA Methylation; Down-Regulation; Esophageal Neoplasms; Female; Gene Expression Regulation, Neoplastic; Humans; Male; Molecular Sequence Data; Polymorphism, Restriction Fragment Length; Promoter Regions, Genetic; RNA, Messenger; Stomach Neoplasms; Trypsin; Trypsinogen