Original Article
Copyright ©2011 Baishideng Publishing Group Co., Limited. All rights reserved.
World J Gastroenterol. Mar 21, 2011; 17(11): 1434-1441
Published online Mar 21, 2011. doi: 10.3748/wjg.v17.i11.1434
Proteomic analysis of pancreatic intraepithelial neoplasia and pancreatic carcinoma in rat models
Lei Wang, Hai-Lin Liu, Ya Li, Ping Yuan
Lei Wang, Hai-Lin Liu, Ya Li, Department of Gastroenterology, the Ninth People’s Hospital Affiliated to the School of Medicine, Shanghai Jiao Tong University, Shanghai 200011, China
Ping Yuan, Department of Pathology, Ruijin Hospital Affiliated to the School of Medicine, Shanghai Jiao Tong University, Shanghai 200025, China
Author contributions: Liu HL designed the study; Wang L and Li Y established animal models and conducted the proteomic research; Yuan P did the the pathological tests; Wang L and Liu HL wrote the manuscript.
Supported by Shanghai Science and Technology Commission, No. 06JC14047
Correspondence to: Hai-Lin Liu, Professor, Department of Gastroenterology, the Ninth People’s Hospital Affiliated to the School of Medicine, Shanghai Jiao Tong University, Shanghai 200011, China. liuhailin@medmail.com.cn
Telephone: +86-21-23271699 Fax: +86-21-63087768
Received: November 4, 2010
Revised: December 16, 2010
Accepted: December 23, 2010
Published online: March 21, 2011
Abstract

AIM: To detect the proteomic variabilities of pancreatic intraepithelial neoplasia (PanIN) and pancreatic carcinoma (PC) induced by 7,12-dimethylbenzanthracene (DMBA) in rat models and to identify potential biomarkers.

METHODS: Sixty adult male Sprague Dawley rats were randomized into three groups. The rats had DMBA implanted into their pancreas for one (n = 20) or two months (n = 20) or assigned to the normal group (n = 20). The rats were killed after one or two months, and were evaluated histopathologically. Three tissue samples from each group of rats with either normal pancreas, PanIN (PanIN-2) or PC were examined by 2D-DIGE. The different expression spot features were analyzed by matrix-assisted laser desorption/ionization-time of flight/time of flight (MALDI-TOF/TOF) tandem mass spectrometry. The expression of enolase 1, a differentially expressed protein, was identified by immunohistochemistry.

RESULTS: There was significant difference in the proportions of neoplastic changes between the 1- and 2-mogroups (P = 0.0488). There was an increase in the frequency of adenocarcinomas in the 2-mo group compared with the 1-mo group (P = 0.0309). No neoplastic changes were observed in any of the animals in the normal group. Enolase 1, pancreatic ELA3B, necdin, Hbp23, CHD3, hnRNP A2/B1, Rap80, and Gnb2l1 were up-regulated in the PanIN and PC tissues, and CEL, TPT1, NME2, PCK2, an unnamed protein product, and glycine C-acetyltransferase were down-regulated in the PanIN and PC tissues. The immunohistochemical results showed that enolase 1 expression was up-regulated in the pancreatic cancer tissues of rats and humans.

CONCLUSION: The pancreatic protein expression changes induced by DMBA suggest potential molecular targets for the early diagnosis and treatment of PC.

Keywords: 7,12-dimethylbenzanthracene; Pancreatic intraepithelial neoplasia; Pancreatic carcinoma; Proteomics