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Tissue-specific gene expression in medullary thyroid carcinoma cells employing calcitonin regulatory elements and AAV vectors

Cancer Gene Therapy volume 8, pages 469–472 (2001)Cite this article

Abstract

Calcitonin (CT), the major secretory product of the C cell, is also expressed in C-cell–derived neoplasia. To investigate the role of the CT gene regulatory sequence in tissue-specific gene expression, the genes coding for the herpes simplex virus thymidine kinase (HSVtk) and for the enhanced green fluorescent protein (EGFP) regulated by the CT promoter (rAAV/CT266tkneo), the CT promoter/enhancer element (rAAV/CTenhtkneo), or the cytomegalovirus (CMV) promoter (rAAV/CMVtkneo) were transduced by recombinant adenoassociated viral (AAV) vectors into the medullary thyroid carcinoma (MTC) cell lines TT and hMTC and into HeLa cells as controls. In TT cell lines and hMTC cell lines transiently infected by the rAAV/CT266tkneo viruses, a significant increase in 3H ganciclovir uptake was observed. Upon ganciclovir treatment, TT cells infected by rAAV/CT266tkneo revealed a significant growth inhibition, which was less tissue-specific because HeLa cells were also affected by these particles (74.5%). In contrast, a minor but more tissue-specific growth inhibition (33.6%) was observed for TT cells after transient infection with the rAAV/CTenhtkneo particles. Employing EGFP controlled by CMV promoter and the individual CT regulatory sequences for transduction by rAAV particles, similar results were obtained indicating that both the CT promoter and enhancer element are required for tissue-specific gene expression in MTC. Cancer Gene Therapy (2001) 8, 469–472

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Acknowledgements

The authors thank Iris Morr, Miriam Mahmut, and Irmgard Preugschat-Gumbrecht for their help in performing this study.

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Authors and Affiliations

  1. Clinical Cooperation Unit Nuclear Medicine, German Cancer Research Center, Heidelberg, Germany

    Shiming Jiang, Annette Altmann, Christine Germann & Uwe Haberkorn

  2. Applied Tumor Virology, German Cancer Research Center, Heidelberg, Germany

    Dirk Grimm & Jürgen A Kleinschmidt

  3. Department of Endocrinology, University of Heidelberg, Heidelberg, Germany

    Tobias Schilling

  4. Department of Nuclear Medicine, University of Heidelberg, Heidelberg, Germany

    Uwe Haberkorn

Authors
  1. Shiming Jiang
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  2. Annette Altmann
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  3. Dirk Grimm
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  4. Jürgen A Kleinschmidt
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  5. Tobias Schilling
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  6. Christine Germann
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  7. Uwe Haberkorn
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Correspondence to Shiming Jiang.

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Jiang, S., Altmann, A., Grimm, D. et al. Tissue-specific gene expression in medullary thyroid carcinoma cells employing calcitonin regulatory elements and AAV vectors. Cancer Gene Ther 8, 469–472 (2001). https://doi.org/10.1038/sj.cgt.7700327

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  • DOI: https://doi.org/10.1038/sj.cgt.7700327

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