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Retrovirus-mediated tk gene therapy of implanted human breast cancer in nude mice under the regulation of Tet-On

Cancer Gene Therapy volume 13, pages 290–297 (2006)Cite this article

Abstract

Tight regulation of the therapeutic gene expression is critical in gene therapy. In this report, a doxycycline (Dox)-regulated retrovirus-mediated gene expression system was used to study the effects of suicide gene therapy on human breast cancer cell line MCF-7 and the nude mice model of implanted human breast cancer. To render the expression of suicide gene under control, we used two pseudoviruses simultaneously, RevTRE/HSVtk and RevTet-On, to infect MCF-7 cells or xenografts of nude mice. When infected by the pseudoviruses and followed by Dox and Ganciclovir (GCV) treatment, MCF-7 cells were arrested at S phase and the growth was suppressed. We then evaluated the antitumor efficiency of this system in vivo through studying the mice bearing human breast cancer xenografts. Compared with control groups, the HSVtk mRNA level increased significantly in tumor tissues, mass of the tumors shrank remarkably, and tumor necrosis features occurred after treatment with Dox and GCV. These data suggest that suicide gene therapy using the Dox-induced Tet-On-controlled HSVtk gene expression system is a feasible method to treat human breast cancer.

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Acknowledgements

This work was supported by the grant from CMB (China Medical Board of New York Inc., Grant # 99-698).

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  1. Molecular Biology Research Center, Xiangya Medical College, Central South University, Changsha, Hunan, P.R. China

    Z-J Zeng, Z-B Li, S-Q Luo & W-X Hu

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Correspondence to W-X Hu.

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Zeng, ZJ., Li, ZB., Luo, SQ. et al. Retrovirus-mediated tk gene therapy of implanted human breast cancer in nude mice under the regulation of Tet-On. Cancer Gene Ther 13, 290–297 (2006). https://doi.org/10.1038/sj.cgt.7700889

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