Transthyretin, identified by proteomics, is overabundant in pancreatic juice from pancreatic carcinoma and originates from pancreatic islets
Transthyretin, identified by proteomics, is overabundant in pancreatic juice from pancreatic carcinoma and originates from pancreatic islets
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DOI：
10.1002/dc.21484
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发表时间：
2011-12-01
影响因子：
1.3
通讯作者：
Ma, Lie
中科院分区：
文献类型：
--
作者：
Lv, Shunli;Gao, Jun;Ma, Lie
通过蛋白质组学对胰液的分析，已经确定了许多在胰腺癌（PC）汁液中过量的蛋白质。这些蛋白质的分泌机制尚不清楚。收集了三种胰腺疾病（PC、慢性胰腺炎（CP）和单纯性胆总管结石（CDS））患者的胰液，并通过2-DE、MALDI-TOF/MS和Western印迹进行分析。用5个PC细胞系、30个PC组织及其相应的邻近胰腺组织来验证编码PC汁中过量蛋白的基因的表达。通过RT-PCR和免疫组化分别测定mRNA和蛋白水平。使用蛋白质组学，证明与CP和CDS相比，PC汁中的蛋白质转甲状腺素蛋白（TTR）上调超过2倍，而载脂蛋白A-I、石抑素和再生胰岛衍生的1 β前体下调超过2倍。Western印迹证实，TTR是过剩的PC汁。然而，TTR mRNA在五种PC细胞系中均未检测到，仅在胰岛细胞中检测到。光镜观察发现，PC组织中胰岛结构几乎完全破坏，胰岛最大直径明显大于正常，PC汁中的一些过量蛋白质，如仅在胰岛中表达的TTR，由于PC组织的增生和结构破坏而泄漏到胰腺导管系统中。肿瘤生长对器官和组织结构的破坏可能导致新的肿瘤标志物，即使这些标志物不是由肿瘤细胞直接分泌的。细胞病理学诊断。2011; 39：875 - 881. (C)2010 Wiley Periodicals，Inc.
Analyses of pancreatic juice by proteomics have identified many proteins that are overabundant in pancreatic cancer (PC) juice. The mechanism by which secretion of these proteins occur remains unclear.Pancreatic juice was collected from patients with three pancreatic diseases: PC, chronic pancreatitis (CP), and simple choledocholithiasis (CDS), and analyzed by 2-DE, MALDI-TOF/MS, and Western blot. Five PC cell lines, 30 PC tissues and their corresponding adjacent pancreatic tissues were used to validate the expression of genes which code for overabundant proteins in PC juice. The mRNA and protein levels were measured by RT-PCR and immunohistochemistry, respectively.Using proteomics, it was demonstrated that the protein transthyretin (TTR) was upregulated more than 2-fold in PC juice compared with CP and CDS, while apolipoprotein A-I, lithostathine, and regenerating islet-derived 1 beta precursor were downregulated more than 2-fold. Western blots confirmed that TTR was overabundant in the PC juice. However, TTR mRNA was not detected in any of the five PC cell lines, and was only detected in islet cells. By microscopy, it was shown that islet architecture was almost completely destroyed, and the islet's maximum diameter appeared larger in PC tissues than in normal.Some overabundant proteins in PC juice, such as TTR expressed only in islets, leak into the pancreatic ductal system due to hyperplasia and architectural damage in PC tissues. The destruction of organ and tissue architecture by tumor growth may result in novel tumor markers even if the markers are not secreted directly by tumor cells. Diagn. Cytopathol. 2011; 39: 875-881. (C) 2010 Wiley Periodicals, Inc.