Twenty-one proteins up-regulated in human H-ras oncogene transgenic rat pancreas cancers are up-regulated in human pancreas cancer

• Published in: Pancreas Vol. 42; no. 6; p. 1034
• Main Authors: Yabushita, Setsuko, Fukamachi, Katsumi, Kikuchi, Fumitake, Ozaki, Masakazu, Miyata, Kaori, Sukata, Tokuo, Deguchi, Yoshihito, Tanaka, Hajime, Kakehashi, Anna, Kawamura, Satoshi, Uwagawa, Satoshi, Wanibuchi, Hideki, Suzui, Masumi, Alexander, David B, Tsuda, Hiroyuki
• Format: Journal Article
• Language: English
• Published: United States 01.08.2013
• Subjects: Adenocarcinoma - genetics; Adenocarcinoma - metabolism; Adenocarcinoma - pathology; Animals; Biomarkers, Tumor - genetics; Biomarkers, Tumor - metabolism; Carcinoma, Pancreatic Ductal - genetics; Carcinoma, Pancreatic Ductal - metabolism; Carcinoma, Pancreatic Ductal - pathology; Chromatography, Liquid; Disease Models, Animal; Feasibility Studies; Humans; Mutation; Pancreatic Neoplasms - genetics; Pancreatic Neoplasms - metabolism; Pancreatic Neoplasms - pathology; Proteins - genetics; Proteins - metabolism; ras Proteins - genetics; ras Proteins - metabolism; Rats; Rats, Transgenic; Tandem Mass Spectrometry; Up-Regulation
• ISSN: 1536-4828
• DOI: 10.1097/mpa.0b013e3182883624

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. 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. 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. 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.