Overexpression of caspase-1 in pancreatic disorders: Implications for a function besides apoptosis

The caspases are known to play a crucial role in the triggering and executi on of apoptosis in a variety of cell types. We assessed the expression of c aspase-1 in 42 pancreatic cancer tissue samples, 38 chronic pancreatitis sp ecimens, and nine normal pancreatic tissues by immunohistochemistry and Wes tern blot analysis. We found a clear overexpression of caspase-1 in both di sorders, but differences in the expression patterns in distinct morphologic compartments. Pancreatic cancer tissue showed a clear cytoplasmatic overex pression of caspase-1 in tumor cells in 71 % of the tumors, whereas normal pancreatic tissue showed only occasional immunoreactivity. In chronic pancr eatitis an overexpression of caspase-1 was found in atrophic acinar cells ( 89%), hyperplastic ducts (87%), and dedifferentiating acinar cells (84%). A lthough in atrophic cells a clear nuclear expression was found, hyperplasti c ducts and dedifferentiating acinar cells showed clear cytoplasmic express ion. Western blot analysis revealed a marked expression of the 45 kDa precu rsor of caspase-1 in pancreatic cancer and chronic pancreatitis (80% and 86 %, respectively). Clear bands at 30 kDa, suggested to represent the p10-p20 heterodimer of active caspase-1, were found in 60% of the cancer tissue an d 14% of the pancreatitis tissue specimens. Since we found a highly signifi cant correlation between cytoplasm overexpression of caspase-1 in pancreati c cancer and overexpression of the known prognostic factors cyclin D1, epid ermal growth factor, and epidermal growth factor receptor, it is plausible that caspase-1 has a yet unknown function in proliferative processes in add ition to its well-known role in the apoptotic pathway.