A tumor-suppressive role for trypsin in human cancer progression.
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.
Department of Otoralyngology-Head and Neck Surgery, The Johns Hopkins University, Baltimore, Maryland 21205, USA.
Keishi
K
Yamashita
Koshi
K
Mimori
Hiroshi
H
Inoue
Masaki
M
Mori
David
D
Sidransky
D000230:Adenocarcinoma / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D001483:Base Sequence; D002294:Carcinoma, Squamous Cell / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D019175:DNA Methylation; D018450:Disease Progression; D015536:Down-Regulation; D004938:Esophageal Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D012150:Polymorphism, Restriction Fragment Length; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D013274:Stomach Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D014357:Trypsin / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D014362:Trypsinogen / Q000096:biosynthesis / Q000235:genetics
D012333:RNA, Messenger; D014362:Trypsinogen; D014357:Trypsin