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  • Acquired Diseases
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Adenovirus-mediated ribozyme targeting of HER-2/neu inhibits in vivo growth of breast cancer cells

Abstract

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.

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Acknowledgements

T Suzuki is supported by the grant from Uehara Memorial Foundation for Research of Life Science, Japan. O Engebraaten is supported by the Norwegian Cancer Society, the US–Norway Fulbright Foundation for Educational Exchange, and the Thomas Fearnley, Heddy and Nils Astrup Foundation. M Kashani-Sabet is supported by the Leaders Society Clinical Career Development Award of the Dermatology Foundation. We thank A Harty for preparing the manuscript. D Curiel is supported by NIH grants ROI-CA60245 and ROI-CA74242.

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Suzuki, T., Anderegg, B., Ohkawa, T. et al. Adenovirus-mediated ribozyme targeting of HER-2/neu inhibits in vivo growth of breast cancer cells. Gene Ther 7, 241–248 (2000). https://doi.org/10.1038/sj.gt.3301065

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