C-JUN and CPP32 (CASPASE 3) in human pancreatic cancer: relation to cell proliferation and death.
BACKGROUND
There is strong evidence that tumor growth is not only a result of uncontrolled cell proliferation but also of decreased apoptosis.


OBJECTIVE
To ascertain the expression of c-Jun in specimens of pancreatic duct cancer and to evaluate its correlation with CPP32, apoptotic index, and proliferation index (MIB-1).


METHODS
Tissue samples were collected from 23 patients with pancreatic duct cancer who had not received chemotherapy nor radiation therapy before surgery. In these specimens we determined the expression of c-Jun protein, CPP32, and MIB-1 by immunohistochemical method. Apoptosis was studied by the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick end labeling method.


RESULTS
CPP32/caspase3 was expressed in 83% and c-Jun in 87% of primary lesions. Three of 23 samples were completely negative for c-Jun, and 4 of 23 were negative for CPP32. Three of 4 specimens negative for CPP32 showed low or negative c-Jun. A significant correlation was found between CPP32/caspase3 and c-Jun (r = 0.51; p < 0.01) and between c-Jun and MIB-1 (r = 0.57; p < 0.004). No correlation was found between CPP32, c-Jun, MIB-1, and apoptotic index.


CONCLUSIONS
The positive correlation between the expression of c-Jun and CPP32 and the absence of both in the same specimens suggest that a common factor or common factors induce the expression of both genes. Pancreatic cancer tissue with an increased percentage of proliferating tumor cells showed also a strong expression of c-Jun, which supports the hypothesis that this oncogene may be involved in the growth of pancreatic cancer. We hypothesize that under different extracellular stimuli both death and proliferation are activated in neoplastic cell, probably under the control of transcription factor AP-1.
Meggiato
Tamara
T
Department of Surgery and Gastroenterology, University of Padova, Italy.
Calabrese
Fiorella
F
De Cesare
Cristina Maria
CM
Baliello
Elisabetta
E
Valente
Marialuisa
M
Del Favero
Giuseppe
G
D000328:Adult; D000368:Aged; D017209:Apoptosis; D021441:Carcinoma, Pancreatic Ductal / Q000378:metabolism* / Q000473:pathology; D053148:Caspase 3; D020169:Caspases / Q000276:immunology / Q000378:metabolism*; D002455:Cell Division; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D019394:Ki-67 Antigen / Q000032:analysis / Q000276:immunology; D008297:Male; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000378:metabolism* / Q000473:pathology; D016755:Proto-Oncogene Proteins c-jun / Q000276:immunology / Q000378:metabolism*
D019394:Ki-67 Antigen; D016755:Proto-Oncogene Proteins c-jun; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases