cIAP2 Overexpression is an early event in pancreatic cancer progression

¹ Institute of Pathology , University of Heidelberg, Germany
² Department of General Surgery, University of Heidelberg, Germany
³ Institute of Pathology, University of Heidelberg, Germany

^* To whom correspondence should be addressed. E-mail: irene_esposito{at}med.uni-heidelberg.de.

Accepted 8 June 2006

	Abstract

Aims: To determine the role of two antiapoptotic proteins of the IAP family, cIAP1 and cIAP2, in human pancreatic carcinogenesis.

Methods: mRNA levels were measured in pancreatic tissues and pancreatic cancer cell lines by quantitative reverse-transcriptase polymerase chain reaction (QRT-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 PanIN lesions, as well as in a subset of primary and metastatic pancreatic ductal adenocarcinomas (PDAC), and a preferential cytoplasmatic localization was observed in the tumor tissues. cIAP1 expression was rare in a cohort of cystic tumors. cIAP2 mRNA levels were significantly higher (2.4 fold) in PDAC than in the normal tissues. cIAP2 protein was overexpressed in PDAC and was detectable in low-grade and high-grade PanIN lesions. Moreover, cIAP2 was frequently expressed in pancreatic cystic tumors. 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 tumors.

Conclusions: cIAP1 might contribute to the regulation of the apoptotic process in the normal and in the neoplastic pancreas, depending on its subcellular localization. cIAP2 overexpression is a frequent and early event in pancreatic cancer progression and could therefore potentially influence important pathophysiological aspects of PDAC, such as anoikis or chemoresistance.

Key Words: PanIN, cIAP1, cIAP2, chronic pancreatitis, pancreatic cancer

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