Reference - Detail
|Author||Yabushita S, Fukamachi K, Kikuchi F, Ozaki M, Miyata K, Sukata T, Deguchi Y, Tanaka H, Kakehashi A, Kawamura S, Uwagawa S, Wanibuchi H, Suzui M, Alexander DB, Tsuda H.|
|Title||Twenty-one proteins up-regulated in human H-ras oncogene transgenic rat pancreas cancers are up-regulated in human pancreas cancer.|
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.
|MeSH||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* Rats Rats, Transgenic Tandem Mass Spectrometry Up-Regulation ras Proteins / genetics ras Proteins / metabolism*|
|WOS Category||GASTROENTEROLOGY & HEPATOLOGY|