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Targeted gene therapy for breast cancer with truncated Bid

Cancer Gene Therapy volume 13, pages 141–149 (2006)Cite this article

Abstract

We studied the efficiency of the proapoptotic factor tBid, targeted to tumor cells using the promoters of the hTERT, Survivin and Muc1 genes, in killing breast cancer cells. tBid is the active fragment of the proapoptotic protein Bid and is generated in response to death receptor activation. When placed under control of a strong CMV promoter, tBid was highly efficient in killing breast cancer cells. When expression of tBid was driven by tumor-specific promoters, the magnitude of killing was significant in cell lines with high levels of promoter activity. For successful gene therapy with targeted tBid, it is therefore crucial to be able to predict promoter activity prior to selection of the therapeutic construct. To test whether gene expression could serve as a predictor, we correlated expression of Survivin, hTERT and Muc1 genes with the activity of the corresponding promoters in a panel of breast cancer cell lines. Expression of the Muc1 gene correlated well with the activity of its promoter and the resultant tumor cell killing. For the hTERT and Survivin promoters, however, promoter activity did not correlate well with the expression of the corresponding genes. The implications and possible mechanism of these discrepancies are discussed.

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Acknowledgements

We thank Dr Satoru Kyo for kindly supplying us with the hTERT promoter constructs. This work was supported by the NIH 5 K12 CA01723-10 Physician Scientist Training Grant and an American Cancer Society Institutional Research Grant.

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Authors and Affiliations

  1. Department of Medicine, Division of Medical Oncology, University of Texas Health Science Center, San Antonio, TX, USA

    I Kazhdan, L Long, R Montellano, D A Cavazos & R A Marciniak

  2. Department of Cellular and Structural Biology, University of Texas Health Science Center, San Antonio, TX, USA

    D A Cavazos & R A Marciniak

  3. South Texas Veterans Health Care System, San Antonio, TX, USA

    R A Marciniak

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Correspondence to I Kazhdan.

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Kazhdan, I., Long, L., Montellano, R. et al. Targeted gene therapy for breast cancer with truncated Bid. Cancer Gene Ther 13, 141–149 (2006). https://doi.org/10.1038/sj.cgt.7700867

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