title: Inhibition of human bladder cancer growth by a suicide gene delivered by JC polyomavirus virus-like particles in a mouse model.
abstract: OBJECTIVE
  Bladder cancer is one of the most common cancers of the urinary tract. The poor 5-year survival rate of invasive bladder cancer represents a challenge for bladder cancer treatment. Previous studies demonstrated that human urothelial carcinoma is susceptible to infection by JC polyomavirus. We used JC polyomavirus virus-like particles to deliver genes into human urothelial carcinoma cells for possible therapeutic investigation.
  
  
  METHODS
  Reporter plasmids (pEGFP-N3) for expressing green fluorescent protein, LacZ expression plasmids bearing cytomegalovirus or Muc1 promoter and a functional plasmid (pUMVC1-tk) for expressing thymidine kinase were packaged into JC polyomavirus virus-like particles. Plasmid DNAs were transduced via the JC polyomavirus virus-like particles into human urothelial carcinoma cells in vitro and into xenografted human bladder tumor nodules in vivo.
  
  
  RESULTS
  pEGFP-N3 DNA was delivered and green fluorescent protein was expressed in human urothelial carcinoma cells in vitro and in the tumor nodules of mice in vivo. The thymidine kinase transgene also functioned in vitro and in vivo after JC polyomavirus virus-like particle transduction. The thymidine kinase gene transduced urothelial carcinoma nodules were drastically reduced in the presence of acyclovir. In addition, we noted selective Muc1-LacZ expression in human urothelial carcinoma cells transduced by JC polyomavirus virus-like particles.
  
  
  CONCLUSIONS
  These findings provide a possible future approach to human urothelial carcinoma gene therapy using JC polyomavirus virus-like particles.
authors.affiliation: Department of Medical Research, Chiayi Christian Hospital, Chiayi, Taiwan, Republic of China.
authors.forename: Chiung-Yao
authors.initials: CY
authors.lastname: Fang
authors.affiliation: Institute of Molecular Biology, National Chung Cheng University, Chiayi, Taiwan, Republic of China.
authors.forename: Yi-Da
authors.initials: YD
authors.lastname: Tsai
authors.affiliation: Department of Urology, Chiayi Christian Hospital, Chiayi, Taiwan, Republic of China; Institute of Molecular Biology, National Chung Cheng University, Chiayi, Taiwan, Republic of China.
authors.forename: Mien-Chun
authors.initials: MC
authors.lastname: Lin
authors.affiliation: Department of Microbiology and Immunology, Chung Shan Medical University, Taichung, Taiwan, Republic of China.
authors.forename: Meilin
authors.initials: M
authors.lastname: Wang
authors.affiliation: Department of Medical Laboratory Science and Biotechnology, Central Taiwan University of Science and Technology, Taichung, Taiwan, Republic of China.
authors.forename: Pei-Lain
authors.initials: PL
authors.lastname: Chen
authors.affiliation: Department of Pediatrics, Chiayi Christian Hospital, Chiayi, Taiwan, Republic of China.
authors.forename: Chun-Nun
authors.initials: CN
authors.lastname: Chao
authors.affiliation: Department of Medical Research, Buddhist Dalin Tzu Chi General Hospital, Chiayi, Taiwan, Republic of China.
authors.forename: Yih-Leh
authors.initials: YL
authors.lastname: Huang
authors.affiliation: Institute of Molecular Biology, National Chung Cheng University, Chiayi, Taiwan, Republic of China. Electronic address: biodcc@ccu.edu.tw.
authors.forename: Deching
authors.initials: D
authors.lastname: Chang
authors.affiliation: Department of Urology, Chiayi Christian Hospital, Chiayi, Taiwan, Republic of China. Electronic address: 01712@cych.org.tw.
authors.forename: Cheng-Huang
authors.initials: CH
authors.lastname: Shen
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D041722:Genes, Transgenic, Suicide; D015316:Genetic Therapy / Q000379:methods; D005822:Genetic Vectors; D006801:Humans; D007577:JC Virus; D051379:Mice; D008819:Mice, Nude; D014407:Tumor Cells, Cultured; D001749:Urinary Bladder Neoplasms / Q000235:genetics* / Q000628:therapy*; D014771:Virion / Q000235:genetics*
keywords: genes; genetic therapy; polyomavirus; suicide; transgenic; urinary bladder neoplasms; virion