Twenty-One Proteins Up-Regulated in Human H-ras Oncogene Transgenic Rat Pancreas Cancers are Up-Regulated in Human Pancreas Cancer
Twenty-One Proteins Up-Regulated in Human H-ras Oncogene Transgenic Rat Pancreas Cancers are Up-Regulated in Human Pancreas Cancer
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DOI：
10.1097/mpa.0b013e3182883624
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发表时间：
2013-08-01
期刊：
影响因子：
2.9
通讯作者：
Tsuda, Hiroyuki
中科院分区：
文献类型：
--
作者：
Yabushita, Setsuko;Fukamachi, Katsumi;Tsuda, Hiroyuki
目的：我们建立了大鼠胰腺导管腺癌(PDAC)模型，在该模型中，受Cre/lox系统调控的人H-ras(G12V)或K-ras(G12V)癌基因的表达促进了胰腺癌的发生。胰腺癌在H-ras(G12V)和K-ras(G12V)转基因大鼠体内发生，在细胞遗传学和组织病理学上与人PDAC相似。本研究旨在确定利用商业上可获得的H-ras(G12V)转基因大鼠寻找人类胰腺癌诊断蛋白质生物标志物的可行性。方法：为了使动物模型用于寻找疾病的蛋白质生物标志物，在该模型中上调的蛋白质在人类中也上调是必不可少的。结果：我们在H-ras(G12V)转基因大鼠PDAC病变中发现了30个上调的蛋白质；重要的是，这30个蛋白质中有21个在人类胰腺癌患者中表达上调。结论：这些结果表明在H-ras(G12V)转基因大鼠PDAC中也有大量上调的蛋白质在人胰腺癌中表达上调，因此，该大鼠模型可用于寻找胰腺癌的诊断生物标志物。
Objectives: We have established rat models of pancreatic ductal adenocarcinoma (PDAC) in which expression of a human H-ras(G12V) or K-ras(G12V) oncogene regulated by the Cre/lox system drives pancreatic carcinogenesis. Pancreatic ductal adenocarcinoma which develops in H-ras(G12V) and K-ras(G12V) transgenic rats is cytogenetically and histopathologically similar to human PDAC. The present study was designed to determine the feasibility of using the commercially available H-ras(G12V) transgenic rat to find diagnostic protein biomarkers for human pancreatic cancer.Methods: For an animal model to be useful for searching for protein biomarkers for a disease, it is essential that proteins that are up-regulated in the model are also up-regulated in humans. We used liquid chromatography-tandem mass spectrometry (LC-MS/MS) to compare H-ras(G12V) transgenic rat PDAC with surrounding normal pancreas tissue.Results: We identified 30 up-regulated proteins in the H-ras(G12V) transgenic rat PDAC lesions; importantly, 21 human homologs of these 30 rat proteins are up-regulated in human pancreatic cancer patients.Conclusions: These results indicate that numerous proteins that are up-regulated in H-ras(G12V) transgenic rat PDAC are also up-regulated in human pancreatic cancer; therefore, this rat model can be used to search for diagnostic biomarkers for this disease.