title: Adenovirus-mediated transduction of ribozymes abrogates HER-2/neu and pleiotrophin expression and inhibits tumor cell proliferation.
abstract: The combination of specific gene targeting technologies with efficient gene delivery systems could provide the means to evaluate the concept of anticancer strategies designed to block expression of potentially rate-limiting tumor promoting factors. Here, we constructed adenoviruses expressing hammerhead-ribozymes targeted to two of these factors, the tyrosine kinase receptor HER-2/neu or the growth factor pleiotrophin (PTN). Adenovirus-mediated transduction of either HER-2/neu- or PTN-targeted ribozymes depleted the respective RNAs and inhibited protein expression significantly in three different human cancer cell lines. This resulted in almost complete abrogation of HER-2/neu- or PTN-dependent cancer-cell proliferation, thus demonstrating the feasibility of this approach as a future cancer gene therapy.
authors.affiliation: Lombardi Cancer Center, Georgetown University, Washington, DC 20007, USA.
authors.forename: F
authors.initials: F
authors.lastname: Czubayko
authors.forename: S G
authors.initials: SG
authors.lastname: Downing
authors.forename: S S
authors.initials: SS
authors.lastname: Hsieh
authors.forename: D J
authors.initials: DJ
authors.lastname: Goldstein
authors.forename: P Y
authors.initials: PY
authors.lastname: Lu
authors.forename: B C
authors.initials: BC
authors.lastname: Trapnell
authors.forename: A
authors.initials: A
authors.lastname: Wellstein
mesh_terms: D000256:Adenoviridae; D002352:Carrier Proteins / Q000235:genetics*; D002455:Cell Division / Q000235:genetics; D016207:Cytokines / Q000235:genetics*; D015870:Gene Expression; D018390:Gene Targeting; D018734:Genes, erbB-2; D015316:Genetic Therapy / Q000379:methods; D005822:Genetic Vectors; D006801:Humans; D008934:Mitogens / Q000235:genetics*; D009369:Neoplasms / Q000628:therapy; D016337:RNA, Catalytic / Q000235:genetics; D014407:Tumor Cells, Cultured
chemical_list: D002352:Carrier Proteins; D016207:Cytokines; D008934:Mitogens; D016337:RNA, Catalytic; C066845:pleiotrophin