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Cancer-specific activation of the survivin promoter and its potential use in gene therapy

Cancer Gene Therapy volume 11, pages 740–747 (2004)Cite this article

Abstract

Survivin is expressed in many cancers but not in normal adult tissues and is transcriptionally regulated. To test the feasibility of using the survivin promoter to induce cancer-specific transgene expression in lung cancer gene therapy, a vector expressing a luciferase gene driven by the survivin promoter was constructed and evaluated in vitro and in vivo. We found that the survivin promoter was generally more highly activated in cancer cell lines than in normal and immortalized normal cell lines. When delivered intravenously by DNA:liposome complexes, the survivin promoter was more than 200 times more cancer specific than the cytomegalovirus promoter in vivo. To identify lung cancer patients who may benefit from gene therapy with the survivin promoter, we measured survivin protein expression in surgical specimens of 75 non-small-cell lung cancers and 10 normal lung tissues by immunohistochemical staining and found that survivin is expressed in most of the non-small-cell lung cancers tested (81%, 61 of 75) but none of the normal lung tissues. The survivin promoter also induced transgene expression of a mutant Bik in cancer cells, which suppressed the growth of cancer cells in vitro and in vivo. These results indicate that the survivin promoter is a cancer-specific promoter for various cancers and that it may be useful in cancer gene therapy.

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Acknowledgements

We thank Dr Stephanie A Miller for helpful discussions. This work was supported by Grants from SPORE in Ovarian Cancer P50CA83639 and SPORE in Pancreatic Cancer P20CA101936 (to M-C Hung). J-S Chen was also supported by a research grant from the National Science Council, Taiwan (NSC 92-2314-B-002-248). (CA 16672) MD Anderson supporting grant.

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  1. Jin-Shing Chen and Jaw-Ching Liu: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, 77030, Texas, USA

    Jin-Shing Chen, Jaw-Ching Liu, Lei Shen, Kung-Ming Rau, Hsu-Ping Kuo, Yan M Li & Mien-Chie Hung

  2. Department of Surgery, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan

    Jin-Shing Chen, Yung-Chie Lee & King-Jen Chang

  3. Department of Pathology, Shanghai Cancer Hospital, Fudan University, Shanghai, China

    Lei Shen & Daren Shi

  4. Division of Hema-Oncology, Chang-Gung Memorial Hospital, Kaohsiung Medical Center, Kaohsiung, Taiwan

    Kung-Ming Rau

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  1. Jin-Shing Chen
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Correspondence to Mien-Chie Hung.

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Chen, JS., Liu, JC., Shen, L. et al. Cancer-specific activation of the survivin promoter and its potential use in gene therapy. Cancer Gene Ther 11, 740–747 (2004). https://doi.org/10.1038/sj.cgt.7700752

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