Reduced expression of ICE/caspase1 and CPP32/caspase3 in human hepatocellular carcinoma.

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.