Overexpression of cellular inhibitor of apoptosis protein 2 is an early event in the progression of pancreatic cancer.
OBJECTIVE
To determine the role of two antiapoptotic proteins of the inhibitor of apoptosis protein family, cellular inhibitor of apoptosis protein 1 (cIAP1) and cellular inhibitor of apoptosis protein 2 (cIAP2), in human pancreatic carcinogenesis.


METHODS
mRNA levels were measured in pancreatic tissues and pancreatic cancer cell lines by quantitative reverse transcriptase PCR. Protein expression was assessed in pancreatic cancer cell lines by immunoblotting and in pancreatic tissues by immunohistochemistry, and correlated with pathological and survival data.


RESULTS
cIAP1 expression was constantly high in non-neoplastic pancreatic tissues, in pancreatic intraepithelial neoplasia (PanIN) lesions, as well as in a subset of primary and metastatic pancreatic ductal adenocarcinomas (PDAC), and a preferential cytoplasmatic localisation was observed in the tumour tissues. cIAP1 expression was rare in a cohort of cystic tumours. cIAP2 mRNA levels were significantly higher (2.4 fold) in PDAC than in normal tissues. cIAP2 protein was overexpressed in PDAC, and was detectable in low- and high-grade PanIN lesions. Moreover, cIAP2 was often expressed in pancreatic cystic tumours. cIAP1 and cIAP2 mRNA and protein were detected in all the examined cell lines. Survival analysis revealed a shorter survival in patients with cIAP1/cIAP2-positive tumours.


CONCLUSIONS
cIAP1 might contribute to the regulation of the apoptotic process in the normal and in the neoplastic pancreas, depending on its subcellular localisation. Overexpression of cIAP2 is a common and early event in the progression of pancreatic cancer, and could therefore potentially influence the important pathophysiological aspects of PDAC, such as anoikis or chemoresistance.
Esposito
Irene
I
Institute of Pathology, University of Heidelberg, Heidelberg, Germany. irene_esposito@med.uni-heidelberg.de
Kleeff
Jörg
J
Abiatari
Ivane
I
Shi
Xined
X
Giese
Nathalia
N
Bergmann
Frank
F
Roth
Wilfried
W
Friess
Helmut
H
Schirmacher
Peter
P
D000230:Adenocarcinoma / Q000737:chemistry / Q000473:pathology; D000328:Adult; D000368:Aged; D002278:Carcinoma in Situ / Q000737:chemistry / Q000473:pathology; D045744:Cell Line, Tumor; D002908:Chronic Disease; D003560:Cysts / Q000737:chemistry; D003593:Cytoplasm / Q000737:chemistry / Q000473:pathology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D051034:Inhibitor of Apoptosis Proteins / Q000032:analysis / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D010179:Pancreas / Q000737:chemistry / Q000473:pathology; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000473:pathology / Q000556:secondary; D010195:Pancreatitis / Q000235:genetics / Q000473:pathology; D012333:RNA, Messenger / Q000032:analysis; D012334:RNA, Neoplasm / Q000032:analysis; D016019:Survival Analysis
D051034:Inhibitor of Apoptosis Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm