Department of Gastroenterology, the Ninth People's Hospital Affiliated to the School of Medicine, Shanghai Jiao Tong University, Shanghai 200011, China.
World J Gastroenterol. 2011 Mar 21;17(11):1434-41. doi: 10.3748/wjg.v17.i11.1434.
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.
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.
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.
The pancreatic protein expression changes induced by DMBA suggest potential molecular targets for the early diagnosis and treatment of PC.
检测 DMBA 诱导的大鼠胰腺上皮内瘤变（PanIN）和胰腺癌（PC）的蛋白质组学变化，并鉴定潜在的生物标志物。
将 60 只成年雄性 Sprague Dawley 大鼠随机分为三组。一组大鼠胰腺内植入 DMBA 1 个月（n = 20）或 2 个月（n = 20），一组设为正常组（n = 20）。1 或 2 个月后处死大鼠，进行组织病理学评估。每组大鼠各取 3 个正常胰腺、PanIN（PanIN-2）或 PC 组织，采用 2D-DIGE 进行检测。基质辅助激光解吸电离飞行时间/飞行时间（MALDI-TOF/TOF）串联质谱分析差异表达点特征。免疫组织化学法鉴定差异表达蛋白烯醇酶 1 的表达情况。
1 个月和 2 个月组之间肿瘤变化的比例有显著差异（P = 0.0488）。与 1 个月组相比，2 个月组腺癌的发生率增加（P = 0.0309）。正常组的动物均未观察到肿瘤变化。烯醇酶 1、胰腺 ELA3B、necdin、Hbp23、CHD3、hnRNP A2/B1、Rap80 和 Gnb2l1 在 PanIN 和 PC 组织中上调，CEL、TPT1、NME2、PCK2、一个未命名的蛋白质产物和甘氨酸 C-乙酰转移酶在 PanIN 和 PC 组织中下调。免疫组化结果显示，大鼠和人胰腺癌组织中烯醇酶 1 的表达上调。
DMBA 诱导的胰腺蛋白表达变化提示了 PC 早期诊断和治疗的潜在分子靶点。
