Overexpression of cellular inhibitor of apoptosis protein 2 is an early event in the progression of pancreatic cancer.

Esposito, Irene and Kleeff, Jörg and Abiatari, Ivane and Shi, Xined and Giese, Nathalia and Bergmann, Frank and Roth, Wilfried and Friess, Helmut and Schirmacher, Peter (2007) Overexpression of cellular inhibitor of apoptosis protein 2 is an early event in the progression of pancreatic cancer. Journal of clinical pathology, 60 (8). pp. 885-95. ISSN 0021-9746

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Abstract

AIM 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.

Item Type: Article
Subjects: R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer)
Depositing User: Dr Ivane Abiatari
Date Deposited: 30 Apr 2015 05:28
Last Modified: 30 Apr 2015 05:28
URI: http://eprints.iliauni.edu.ge/id/eprint/2211

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