Adenovirus-mediated ribozyme targeting of HER-2/neu inhibits in vivo growth of breast cancer cells.
HER-2/neu is overexpressed in 25-30% of human breast cancers. We prepared an anti-HER-2/neu hammerhead ribozyme expressed by a recombinant adenovirus (rAdHER-Rz). Human breast cancer cell lines were transduced with high efficiency, resulting in decreased HER-2/neu expression. In vivo injections of rAdHER-Rz into BT-474 tumors established in nude mice inhibited tumor growth to 20% of mock-treated controls. Similar in vivo effects were shown in MCF-7 cells, which do not overexpress HER-2/neu. The growth inhibitory effects of rAdHER-Rz were greater than those of an antisense-expressing vector. These results suggest the utility of anti-HER-2/neu ribozymes as a rational strategy for gene therapy of breast cancer. Gene Therapy (2000) 7, 241-248.
Suzuki
T
T
Cancer Research Department, Berlex Biosciences, Richmond, CA, USA.
Anderegg
B
B
Ohkawa
T
T
Irie
A
A
Engebraaten
O
O
Halks-Miller
M
M
Holm
P S
PS
Curiel
D T
DT
Kashani-Sabet
M
M
Scanlon
K J
KJ
D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D001483:Base Sequence; D001943:Breast Neoplasms / Q000473:pathology / Q000628:therapy*; D002455:Cell Division; D018390:Gene Targeting / Q000379:methods*; D018734:Genes, erbB-2 / Q000235:genetics*; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction / Q000379:methods; D016337:RNA, Catalytic / Q000235:genetics; D014407:Tumor Cells, Cultured
D016337:RNA, Catalytic; C121505:Rz967