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

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

doi:10.1038/sj.gt.3301065

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

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

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66 Scopus citations

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 HER2/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.

Original language	English
Pages (from-to)	241-248
Number of pages	8
Journal	Gene therapy
Volume	7
Issue number	3
DOIs	https://doi.org/10.1038/sj.gt.3301065
State	Published - Feb 2000

Keywords

BT-474
Gene therapy
HER-2/neu
Recombinant adenovirus
Ribozymes

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title = "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 HER2/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.",

keywords = "BT-474, Gene therapy, HER-2/neu, Recombinant adenovirus, Ribozymes",

author = "T. Suzuki and B. Anderegg and T. Ohkawa and A. Irie and O. Engebraaten and M. Halks-Miller and Holm, {P. S.} and Curiel, {D. T.} and M. Kashani-Sabet and Scanlon, {K. J.}",

note = "Funding Information: 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.",

year = "2000",

month = feb,

doi = "10.1038/sj.gt.3301065",

language = "English",

volume = "7",

pages = "241--248",

journal = "Gene therapy",

issn = "0969-7128",

number = "3",

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T1 - Adenovirus-mediated ribozyme targeting of HER-2/neu inhibits in vivo growth of breast cancer cells

AU - Suzuki, T.

AU - Anderegg, B.

AU - Ohkawa, T.

AU - Irie, A.

AU - Engebraaten, O.

AU - Halks-Miller, M.

AU - Holm, P. S.

AU - Curiel, D. T.

AU - Kashani-Sabet, M.

AU - Scanlon, K. J.

N1 - Funding Information: 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.

PY - 2000/2

Y1 - 2000/2

N2 - 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 HER2/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.

AB - 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 HER2/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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KW - Gene therapy

KW - HER-2/neu

KW - Recombinant adenovirus

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DO - 10.1038/sj.gt.3301065

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AN - SCOPUS:0033993508

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EP - 248

JO - Gene therapy

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ER -

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

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