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Expression in UVW glioma cells of the noradrenaline transporter gene, driven by the telomerase RNA promoter, induces active uptake of [131I]MIBG and clonogenic cell kill

Oncogene volume 20, pages 7804–7808 (2001)Cite this article

Abstract

One of the most effective ways to kill cancer cells is by treatment of tumours with radiation. However, the administered dose of radiation to the tumour is limited by normal tissue toxicity. Strategies which decrease normal tissue exposure relative to tumour dose are urgently sought. One such promising scheme involves gene transfer, leading to the introduction of transporters specific for pharmaceuticals which can be labelled with radionuclides. We have previously demonstrated in vitro, that transfer of the noradrenaline transporter (NAT) gene, under viral promoter control, induces in host cells the active accumulation of the radiopharmaceutical [131I]meta-iodobenzylguanidine ([131I]MIBG) which results in kill of clonogens. We now report 17-fold enhancement of [131I]MIBG uptake by UVW glioma cells transfected with the NAT gene whose expression is driven by the human telomerase RNA (hTR) promoter (70% the uptake achieved by the strong viral promoter). Multicellular spheroids composed of hTR–NAT-transfected UVW cells exhibited dose-dependent susceptibility to treatment with [131I]MIBG. This was demonstrated by decreased survival of clonogens and complete sterilization of clonogens derived from spheroids and also failure of spheroids to regrow after administration of 7 MBq/ml [131I]MIBG. These data suggest hTR regulated expression of NAT may be an effective gene therapy strategy.

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Acknowledgements

The authors would like to thank Aileen Monaghan for practical advice and technical support. Thanks also to Professor Heinz Bonish and Dr Michael Bruss of the University of Bonn for the kind gift of the NAT cDNA. This work is supported primarily by The Cancer Research Campaign and thanks also to The Department of Health, Department of Clinical Physics, Glasgow University, The Neuroblastoma Society and SHERT for additional funding.

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Authors and Affiliations

  1. Department of Radiation Oncology, University of Glasgow, CRC Beatson Laboratories, Garscube Estate, Bearsden, Glasgow, G61 1BD, UK

    Marie Boyd, Robert J Mairs, Susan C Mairs, Lesley Wilson, Anne Livingstone, Shona H Cunningham, Mary M Brown & Marlynne Quigg

  2. Department of Child Health, Yorkhill Hospital, Glasgow, UK

    Robert J Mairs & Shona H Cunningham

  3. Department of Clinical Physics, Beatson Oncology Centre, Western Infirmary, Glasgow, UK

    Lesley Wilson & Anne Livingstone

  4. Department of Urology, Gartnavel Hospital, Glasgow, UK

    Mary M Brown

  5. CRC Department of Medical Oncology, University of Glasgow, CRC Beatson Laboratories, Garscube Estate, Switchback Road, Bearsden, Glasgow, G61 1BD, UK

    W Nicol Keith

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  1. Marie Boyd
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  2. Robert J Mairs
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Correspondence to Marie Boyd.

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Boyd, M., Mairs, R., Mairs, S. et al. Expression in UVW glioma cells of the noradrenaline transporter gene, driven by the telomerase RNA promoter, induces active uptake of [131I]MIBG and clonogenic cell kill. Oncogene 20, 7804–7808 (2001). https://doi.org/10.1038/sj.onc.1204955

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