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Loss of caspase-1 gene expression in human gastric carcinomas and cell lines
Chang Do Jee1, Hye Seung Lee, Soo In Bae
1Cancer Research Institute, Seoul National University College of Medicine, Seoul 110-799, Korea.
Abstract:
The caspases are a family of aspartic acid-specific proteases that fulfill varied and often critical roles in mammalian apoptosis or in the proteolytic activation of cytokines. Caspase-1 (interleukin-1beta-converting enzyme) is a member of the cysteine protease family, which cleaves target proteins following aspartic acid residues. We investigated caspase-1 expression in stomach cancer, tissues and cell lines. Of 301 consecutive gastric carcinomas, 58 cases (19.3%) showed the expressional loss of caspase-1. Loss of caspase-1 expression was significantly associated with pTNM stage (p=0.03), lymph node metastasis (p=0.01) and patient survival (p<0.01). Caspase-1 expression was also significantly correlated in an inverse manner with p53 expression (p<0.01). Among the 11 gastric cancer cell lines examined, three cell lines showed loss of expression at the protein and mRNA levels. On treatment with 5-aza-2'-deoxycytidine (5-aza-C), and/or trichostatin A (TSA), all three cell lines re-expressed caspase-1 mRNA. The above findings suggest that epigenetic events such as DNA methylation and histone deacetylation play important roles in the regulation of caspase-1, and that loss of caspase-1 expression is associated with poor survival in gastric carcinoma.
Insights
Loss of caspase-1 expression in stomach cancer is linked to advanced disease and poor survival. Epigenetic changes, like DNA methylation, may cause this loss, suggesting potential therapeutic targets for gastric carcinoma.
Area of Science:
- Molecular Biology
- Oncology
- Biochemistry
Background:
- Caspases are crucial proteases in apoptosis and cytokine activation.
- Caspase-1 (interleukin-1beta-converting enzyme) is a cysteine protease.
- Its role in gastric cancer requires further investigation.
Purpose of the Study:
- To investigate caspase-1 expression in gastric cancer tissues and cell lines.
- To determine the association between caspase-1 loss and clinicopathological features.
- To explore the potential epigenetic regulation of caspase-1 in gastric cancer.
Main Methods:
- Analysis of caspase-1 expression in 301 gastric carcinomas and 11 cell lines.
- Correlation analysis with pTNM stage, lymph node metastasis, patient survival, and p53 expression.
- Treatment of cell lines with epigenetic modifiers (5-aza-C, TSA) to assess caspase-1 re-expression.
Main Results:
- 19.3% of gastric carcinomas showed loss of caspase-1 expression.
- Loss of caspase-1 was significantly associated with advanced pTNM stage, lymph node metastasis, and poorer patient survival.
- Inverse correlation observed between caspase-1 and p53 expression.
- Three cell lines exhibited loss of caspase-1 at protein and mRNA levels, which was reversed by 5-aza-C and TSA treatment.
Conclusions:
- Loss of caspase-1 expression is a significant indicator of poor prognosis in gastric carcinoma.
- Epigenetic mechanisms, including DNA methylation and histone deacetylation, likely regulate caspase-1 expression.
- Targeting these epigenetic events may offer therapeutic strategies for gastric cancer.
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