Adenovirus-mediated ribozyme targeting of HER-2/neu inhibits in vivo growth of breast cancer cells
Gene Therapy, February 2000
T Suzuki, B Anderegg, T Ohkawa, A Irie, O Engebraaten, M Halks-Miller, P S Holm, D T Curiel, M Kashani-Sabet, K J Scanlon
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.
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