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Reduced expression of ICE/caspase1 and CPP32/caspase3 in human hepatocellular carcinoma
K Fujikawa1, K Shiraki, K Sugimoto
1First Department of Internal Medicine, Mie University School of Medicine, Japan.
Abstract:
The interleukin-1(-converting enzymes (ICE)/caspase1 and the CPP32/caspase3, cysteine proteases, play an important role in the maintenance of homeostasis by inducing apoptosis. Since human hepatocellular carcinomas (HCCs) demonstrate strong resistance to apoptosis, we investigated the expression of ICE and CPP32 in human HCCs. Reverse transcription PCR analysis revealed that one out of five HCC tissues showed no band of ICE mRNA and two out of five HCC tissues showed no band of CPP32 mRNA. An immunohistochemical study of 20 cases of HCC tissues and non-tumor parts revealed that immunoreactivity of ICE and CPP32 was preferentially observed in the cytoplasm, appearing as a diffuse and homogeneous pattern. Some nuclei also stained with anti-ICE antibody or anti-CPP32 antibody and demonstrated apoptotic features. Overall, the expression of ICE and CPP32 were significantly down-regulated in the HCCs compared to nontumor cells. In situ nick end labeling method (TUNEL) labeling index significantly decreased according to the decreasing staining intensity of CPP32. However, there was no tendency for the TUNEL labeling index to decrease with decreasing ICE staining intensity. Our results suggested that the expression of ICE and CPP32 were down-regulated and that especially reduced expression of CPP32 may contribute to resistance against apoptosis in human HCCs.
Insights
Expression of key apoptosis-inducing enzymes, interleukin-1-converting enzyme (ICE)/caspase-1 and CPP32/caspase-3, is reduced in human hepatocellular carcinomas (HCCs). This downregulation, particularly of CPP32, may drive HCCs
Area of Science:
- Molecular Biology
- Cellular Biology
- Oncology
Background:
- Interleukin-1-converting enzyme (ICE)/caspase-1 and CPP32/caspase-3 are cysteine proteases crucial for apoptosis and homeostasis.
- Human hepatocellular carcinomas (HCCs) exhibit significant resistance to apoptosis, a key process for preventing tumor development.
Purpose of the Study:
- To investigate the expression levels of ICE and CPP32 in human HCC tissues.
- To determine the correlation between ICE and CPP32 expression and apoptosis resistance in HCC.
Main Methods:
- Reverse transcription PCR (RT-PCR) was used to analyze ICE and CPP32 mRNA expression in HCC tissues.
- Immunohistochemistry was employed to assess ICE and CPP32 protein expression and localization in HCC and adjacent non-tumor tissues.
- In situ nick end labeling (TUNEL) assay was performed to evaluate apoptosis levels.
Main Results:
- Downregulation of both ICE and CPP32 expression was observed in HCC tissues compared to non-tumor tissues.
- Reduced CPP32 staining intensity correlated significantly with a decreased TUNEL labeling index, indicating reduced apoptosis.
- No significant correlation was found between ICE staining intensity and the TUNEL labeling index.
Conclusions:
- The expression of ICE and CPP32 is significantly reduced in human HCCs.
- The decreased expression of CPP32, in particular, may contribute to the apoptosis resistance characteristic of HCC.
- Targeting CPP32 could be a potential therapeutic strategy for overcoming apoptosis resistance in HCC.