title: A cultured approach to canine urothelial carcinoma: molecular characterization of five cell lines.
abstract: BACKGROUND
  Urothelial carcinoma (UC), also known as transitional cell carcinoma (TCC), of the bladder is the most common neoplasm affecting the canine urogenital system. To facilitate study of the disease in vitro, cell line models have been established from primary tumor biopsies. Their resemblance to the primary disease, however, has not been well defined. In the present study, we evaluated five canine UC cell lines via oligonucleotide array comparative genomic hybridization (oaCGH), fluorescence in situ hybridization (FISH), and gene expression analysis.
  
  
  RESULTS
  Comparison of genome wide DNA copy number profiles of the cell lines with primary biopsy specimens revealed redundancies in genomic aberrations, indicating that the cell lines retain the gross genomic architecture of primary tumors. As in the primary tumors, gain of canine chromosomes 13 and 36 and loss of chromosome 19 were among the most frequent aberrations evident in the cell lines. FISH analysis revealed chromosome structural aberrations, including tandem duplications, bi-armed chromosomes, and chromosome fusions, suggesting genome instability during neoplastic transformation. Gene expression profiling highlighted numerous differentially expressed genes, including many previously shown as dysregulated in primary canine UC and human bladder cancer. Pathway enrichment analysis emphasized pathways suspected to be at the crux of UC pathogenesis, including xenobiotic and lipid compound metabolism.
  
  
  CONCLUSIONS
  These data support valid use of the canine UC cell lines evaluated by confirming they provide an accurate and practical means to interrogate the UC at a molecular level. Moreover, the cell lines may provide a valuable model for furthering our understanding of aberrant metabolic pathways in UC development.
authors.affiliation: Department of Molecular Biomedical Sciences, College of Veterinary Medicine, North Carolina State University, 1060 William Moore Drive, Raleigh, NC 27607 USA.
authors.forename: S G
authors.initials: SG
authors.lastname: Shapiro
authors.affiliation: Department of Veterinary Clinical Sciences, Purdue University, College of Veterinary Medicine, West Lafayette, IN USA ; Purdue University Center for Cancer Research, West Lafayette, IN USA.
authors.forename: D W
authors.initials: DW
authors.lastname: Knapp
authors.affiliation: Department of Molecular Biomedical Sciences, College of Veterinary Medicine, North Carolina State University, 1060 William Moore Drive, Raleigh, NC 27607 USA ; Center for Comparative Medicine and Translational Research, North Carolina State University, Raleigh, NC USA ; Center for Human Health and the Environment, North Carolina State University, Raleigh, NC USA ; Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC USA.
authors.forename: Matthew
authors.initials: M
authors.lastname: Breen
keywords: Bladder cancer; Cell lines; Chromosome; Lipid metabolism; Transitional cell carcinoma; Urothelial carcinoma