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Loss of Rho function in the thymus is accompanied by the development of thymic lymphoma

Oncogene volume 19, pages 13–20 (2000)Cite this article

Abstract

In vitro studies in model cell lines have implicated the GTPase Rho in the control of diverse cellular responses including the control of the actin cytoskeleton and the regulation of cell cycle progression. It is also reported that the transformation of fibroblasts via oncogenic Ras requires intact Rho signalling. An invaluable tool used to investigate Rho function is the bacterial toxin C3 transferase derived from Clostridium botulinum. C3 transferase ribosylates Rho in its effector domain thereby abolishing interaction with downstream effectors. We have previously reported the use of C3 transferase under the control of the thymocyte specific lck promoter to explore the role of Rho in T cell biology. Strikingly, lck-C3 mice develop aggressive malignant thymic lymphoblastic lymphomas between 4 and 8 months of age. These studies reveal that loss of Rho function is associated with prediposition to lymphoid cell transformation. Inhibition of Rho function has been suggested as a therapeutic strategy for treatment of Ras-transformed tumours. The development of lymphomas in mice devoid of functional Rho in their T cell compartment shows that such a strategy would need to be used with caution.

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Acknowledgements

We wish to thank Ian Rosewell for injection of transgenic constructs, Tracy Grafton, Sam Hoskins, Julie Bee and Gillian Hutchinson for animal care, George Elia and Robert Hasserjian for histological preparations and analysis. This work was supported by the Imperial Cancer Research Fund. PS Costello is funded by the EEC Biotech Program (28305) SC Cleverley is supported by the ICRF and the Yamanouchi Research Institute. SW Henning was supported by the European Community Training and Mobility of Researchers Program (ERBFMICT 960518).

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  1. S W Henning

    Present address: Department of Molecular and Cell Biology, Howard Hughes Medical Institute, University of California at Berkeley, Berkeley, 94720-3200, California, CA, USA

  2. S C Cleverley and P S Costello: SC Cleverley and PS Costello contributed equally to this manuscript

Authors and Affiliations

  1. Lymphocyte Activation Laboratory, Imperial Cancer Research Fund, 44 Lincoln's Inn Fields, London, WC2A 3PX, UK

    S C Cleverley, P S Costello, S W Henning & D A Cantrell

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  1. S C Cleverley
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Cleverley, S., Costello, P., Henning, S. et al. Loss of Rho function in the thymus is accompanied by the development of thymic lymphoma. Oncogene 19, 13–20 (2000). https://doi.org/10.1038/sj.onc.1203259

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