Adenovirus-mediated transduction of ribozymes abrogates HER-2/neu and pleiotrophin expression and inhibits tumor cell proliferation.
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.
Czubayko
F
F
Lombardi Cancer Center, Georgetown University, Washington, DC 20007, USA.
Downing
S G
SG
Hsieh
S S
SS
Goldstein
D J
DJ
Lu
P Y
PY
Trapnell
B C
BC
Wellstein
A
A
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
D002352:Carrier Proteins; D016207:Cytokines; D008934:Mitogens; D016337:RNA, Catalytic; C066845:pleiotrophin