Establishment of an Orthotopic Mouse Non-Muscle Invasive Bladder Cancer Model Expressing the Mammalian Target of Rapamycin Signaling Pathway.
10.3346/jkms.2014.29.3.343
- Author:
Soon Ja KIM
1
;
Ho Kyung SEO
;
Hye Hyun SEO
;
Sang Jin LEE
;
Jong Kyou KWON
;
Tae Jin LEE
;
Byung Hoon CHI
;
In Ho CHANG
Author Information
1. Biomedical Science, Department of Medicine, Chung-Ang University Graduate School, Seoul, Korea.
- Publication Type:Original Article ; Research Support, Non-U.S. Gov't
- Keywords:
Urinary Bladder Neoplasms;
Mouse Orthotopic Model;
mTOR
- MeSH:
Animals;
Blotting, Western;
Cell Line, Tumor;
Disease Models, Animal;
Female;
Genes, Reporter;
Green Fluorescent Proteins/genetics/metabolism;
Humans;
Immunohistochemistry;
Luciferases, Firefly/genetics;
Luminescent Measurements;
Mice;
Mice, Nude;
Neoplasm Staging;
*Signal Transduction;
TOR Serine-Threonine Kinases/*metabolism;
Transplantation, Heterologous;
Urinary Bladder Neoplasms/*metabolism/pathology/veterinary
- From:Journal of Korean Medical Science
2014;29(3):343-350
- CountryRepublic of Korea
- Language:English
-
Abstract:
We established an orthotopic non-muscle invasive bladder cancer (NMIBC) mouse model expressing the mammalian target of the rapamycin (mTOR) signaling pathway. After intravesical instillation of KU-7-lucs (day 0), animals were subsequently monitored by bioluminescence imaging (BLI) on days 4, 7, 14, and 21, and performed histopathological examination. We also validated the orthotopic mouse model expressing the mTOR signaling pathway immunohistochemically. In vitro BLI photon density was correlated with KU-7-luc cell number (r2 = 0.97, P < 0.01) and in vivo BLI photon densities increased steadily with time after intravesical instillation. The tumor take rate was 84.2%, formed initially on day 4 and remained NMIBC up to day 21. T1 photon densities were significantly higher than Ta (P < 0.01), and histological tumor volume was positively correlated with BLI photon density (r2 = 0.87, P < 0.01). The mTOR signaling pathway-related proteins were expressed in the bladder, and were correlated with the western blot results. Our results suggest successful establishment of an orthotopic mouse NMIBC model expressing the mTOR signaling pathway using KU-7-luc cells. This model is expected to be helpful to evaluate preclinical testing of intravesical therapy based on the mTOR signaling pathway against NMIBC.
