Related Experiment Videos
A tumor-suppressive role for trypsin in human cancer progression
Keishi Yamashita1, Koshi Mimori, Hiroshi Inoue
1Department of Otoralyngology-Head and Neck Surgery, The Johns Hopkins University, Baltimore, Maryland 21205, USA.
Abstract:
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.
Insights
Trypsin gene expression is reduced in esophageal and gastric cancers, often due to promoter hypermethylation. This suggests trypsin may act as a tumor suppressor in human carcinomas.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Trypsin, a serine protease, is implicated in cancer invasion.
- Understanding trypsinogen's role in carcinoma is crucial for cancer research.
Purpose of the Study:
- To investigate trypsinogen expression in esophageal squamous cell carcinoma (ESCC) and gastric adenocarcinoma.
- To determine the correlation between trypsinogen expression, promoter methylation, and cancer progression.
Main Methods:
- RNA expression analysis in 49 ESCC and 72 gastric adenocarcinoma tissues.
- Bisulfite DNA sequencing and methylation-specific PCR to assess promoter hypermethylation.
- Analysis of PAR2 expression and tumor invasion in gastric cancer.
Main Results:
- Reduced trypsinogen expression observed in 95% of primary ESCC and 9/13 ESCC cell lines.
- Trypsinogen silencing correlated with promoter hypermethylation in ESCC.
- Reduced trypsinogen and PAR2 expression in gastric adenocarcinomas linked to increased tumor penetration (P = 0.001).
Conclusions:
- Trypsinogen expression is frequently downregulated in human carcinomas.
- Promoter hypermethylation is a key mechanism for trypsinogen silencing in ESCC.
- Findings support a tumor-suppressive role for trypsin in human carcinoma.