title: Comparison of prostate-specific promoters and the use of PSP-driven virotherapy for prostate cancer.
abstract: Prostate cancer is the most frequently diagnosed cancer and the second leading cause of cancer deaths in men today. Although virus-based gene therapy is a promising strategy to combat advanced prostate cancer, its current effectiveness is limited partially due to inefficient cellular transduction in vivo. To overcome this obstacle, conditional oncolytic viruses (such as conditional replication adenovirus (CRAD)) are developed to specifically target prostate without (or with minimal) systemic toxicity due to viral self-replication. In this study, we have analyzed and compared three prostate-specific promoters (PSA, probasin, and MMTV LTR) for their specificity and activity both in vitro and in vivo. Both mice model with xenograft prostate tumor model and canine model were used. The best PSP was selected to construct a prostate-specific oncolytic adenovirus (CRAD) by controlling the adenoviral E1 region. The efficacy and specificity of CRAD on prostate cancer cells were examined in cell culture and animal models.
authors.affiliation: Department of Pathology and Laboratory Medicine, The University of Tennessee Health Science Center, Cancer Research Building, Room 218, 19 South Manassas Street, Memphis, TN 38163, USA. ylu@uthsc.edu
authors.forename: Yi
authors.initials: Y
authors.lastname: Lu
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhang
authors.forename: Guimin
authors.initials: G
authors.lastname: Chang
authors.forename: Jun
authors.initials: J
authors.lastname: Zhang
mesh_terms: D000256:Adenoviridae; D000727:Androgen-Binding Protein / Q000235:genetics; D000818:Animals; D045744:Cell Line, Tumor; D004285:Dogs; D006801:Humans; D008297:Male; D008324:Mammary Tumor Virus, Mouse / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D050130:Oncolytic Virotherapy / Q000379:methods*; D050504:Oncolytic Viruses; D011401:Promoter Regions, Genetic; D017430:Prostate-Specific Antigen / Q000235:genetics; D011471:Prostatic Neoplasms / Q000473:pathology / Q000628:therapy*; D051381:Rats; D020079:Terminal Repeat Sequences / Q000235:genetics
chemical_list: D000727:Androgen-Binding Protein; C027519:probasin; D017430:Prostate-Specific Antigen