An animal model of preclinical diagnosis of pancreatic ductal adenocarcinomas.
Pancreatic ductal adenocarcinoma (PDA) is a highly lethal disease, which is usually diagnosed in an advanced stage. Animal PDA models which reflect the human condition are clearly necessary to develop early diagnostic tools and explore new therapeutic approaches. We have established transgenic rats carrying a mutated H- or K-ras gene (Hras250 and Kras327) controlled by Cre/loxP activation. These animals develop PDA which are histopathologically similar to that in humans. We utilized this model to identify biomarkers to detect early PDA. We report here that serum levels of Erc/Mesothelin are significantly higher in rats bearing PDA than in controls. Importantly, the levels are significantly elevated in rats before grossly visible carcinomas develop. Even in rats with very small microscopic ductal carcinoma lesions, elevated serum Erc/Mesothelin can be detected. We believe this is the first report of a pancreas tumor animal model in which pre-symptomatic lesions can be diagnosed.
Fukamachi
Katsumi
K
Department of Molecular Toxicology, Nagoya City University Graduate School of Medical Sciences, Nagoya 467-8601, Japan.
Tanaka
Hajime
H
Hagiwara
Yoshiaki
Y
Ohara
Hirotaka
H
Joh
Takashi
T
Iigo
Masaaki
M
Alexander
David B
DB
Xu
Jiegou
J
Long
Ne
N
Takigahira
Misato
M
Yanagihara
Kazuyoshi
K
Hino
Okio
O
Saito
Izumu
I
Tsuda
Hiroyuki
H
D000818:Animals; D014408:Biomarkers, Tumor / Q000097:blood*; D021441:Carcinoma, Pancreatic Ductal / Q000097:blood / Q000175:diagnosis* / Q000473:pathology; D004195:Disease Models, Animal; D005260:Female; D058851:GPI-Linked Proteins; D011905:Genes, ras / Q000235:genetics; D006801:Humans; D008562:Membrane Glycoproteins / Q000097:blood*; D000090204:Mesothelin; D010190:Pancreatic Neoplasms / Q000097:blood / Q000175:diagnosis* / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D055647:Rats, Transgenic
D014408:Biomarkers, Tumor; D058851:GPI-Linked Proteins; D008562:Membrane Glycoproteins; C000715529:Msln protein, rat; D000090204:Mesothelin