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 execution of apoptosis in a variety of cell types. We assessed the expression of caspase-1 in 42 pancreatic cancer tissue samples, 38 chronic pancreatitis specimens, and nine normal pancreatic tissues by immunohistochemistry and Western blot analysis. We found a clear overexpression of caspase-1 in both disorders, but differences in the expression patterns in distinct morphologic compartments. Pancreatic cancer tissue showed a clear cytoplasmatic overexpression of caspase-1 in tumor cells in 71% of the tumors, whereas normal pancreatic tissue showed only occasional immunoreactivity. In chronic pancreatitis an overexpression of caspase-1 was found in atrophic acinar cells (89%), hyperplastic ducts (87%), and dedifferentiating acinar cells (84%). Although in atrophic cells a clear nuclear expression was found, hyperplastic ducts and dedifferentiating acinar cells showed clear cytoplasmic expression. Western blot analysis revealed a marked expression of the 45 kDa precursor 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 and 14% of the pancreatitis tissue specimens. Since we found a highly significant correlation between cytoplasm overexpression of caspase-1 in pancreatic cancer and overexpression of the known prognostic factors cyclin D1, epidermal growth factor, and epidermal growth factor receptor, it is plausible that caspase-1 has a yet unknown function in proliferative processes in addition to its well-known role in the apoptotic pathway.
Ramadani
M
M
Department of General Surgery, University of Ulm, Steinhövelstrasse 9, 89075 Ulm, Germany.
Gansauge
F
F
Schlosser
S
S
Yang
Y
Y
Beger
H G
HG
Gansauge
S
S
D017209:Apoptosis; D015153:Blotting, Western; D016022:Case-Control Studies; D020170:Caspase 1 / Q000096:biosynthesis* / Q000502:physiology; D002908:Chronic Disease; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D010179:Pancreas / Q000201:enzymology; D010190:Pancreatic Neoplasms / Q000201:enzymology*; D010195:Pancreatitis / Q000201:enzymology*
D020170:Caspase 1