title: Establishment of an orthotopic mouse non-muscle invasive bladder cancer model expressing the mammalian target of rapamycin signaling pathway.
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 (r (2) = 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 (r (2) = 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.
authors.affiliation: Biomedical Science, Department of Medicine, Chung-Ang University Graduate School, Seoul, Korea.
authors.forename: Soon-Ja
authors.initials: SJ
authors.lastname: Kim
authors.affiliation: Center for Prostate Cancer, Research Institute National Cancer Center, Goyang, Korea.
authors.forename: Ho Kyung
authors.initials: HK
authors.lastname: Seo
authors.affiliation: Genitourinary Cancer Branch, Research Institute National Cancer Center, Goyang, Korea.
authors.forename: Hye-Hyun
authors.initials: HH
authors.lastname: Seo
authors.affiliation: Genitourinary Cancer Branch, Research Institute National Cancer Center, Goyang, Korea.
authors.forename: Sang-Jin
authors.initials: SJ
authors.lastname: Lee
authors.affiliation: Department of Urology, Chung-Ang University College of Medicine, Seoul, Korea.
authors.forename: Jong Kyou
authors.initials: JK
authors.lastname: Kwon
authors.affiliation: Department of Pathology, Chung-Ang University College of Medicine, Seoul, Korea.
authors.forename: Tae-Jin
authors.initials: TJ
authors.lastname: Lee
authors.affiliation: Department of Urology, Chung-Ang University College of Medicine, Seoul, Korea.
authors.forename: Byung Hoon
authors.initials: BH
authors.lastname: Chi
authors.affiliation: Department of Urology, Chung-Ang University College of Medicine, Seoul, Korea.
authors.forename: In Ho
authors.initials: IH
authors.lastname: Chang
mesh_terms: D000818:Animals; D015153:Blotting, Western; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D005260:Female; D017930:Genes, Reporter; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D049409:Luciferases, Firefly / Q000235:genetics; D008163:Luminescent Measurements; D051379:Mice; D008819:Mice, Nude; D009367:Neoplasm Staging; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*; D014183:Transplantation, Heterologous; D001749:Urinary Bladder Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000662:veterinary
chemical_list: D049452:Green Fluorescent Proteins; D049409:Luciferases, Firefly; D058570:TOR Serine-Threonine Kinases
keywords: Mouse Orthotopic Model; Urinary Bladder Neoplasms; mTOR