Loss of Rho function in the thymus is accompanied by the development of thymic lymphoma.
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.
Cleverley
S C
SC
Lymphocyte Activation Laboratory, Imperial Cancer Research Fund, 44 Lincoln's Inn Fields, London WC2A 3PX, UK.
Costello
P S
PS
Henning
S W
SW
Cantrell
D A
DA
D036002:ADP Ribose Transferases / Q000502:physiology; D000818:Animals; D001905:Botulinum Toxins; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / Q000502:physiology; D008223:Lymphoma / Q000209:etiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D008822:Mice, Transgenic; D013950:Thymus Gland / Q000502:physiology*; D013953:Thymus Neoplasms / Q000209:etiology*; D020741:rho GTP-Binding Proteins / Q000502:physiology*
D036002:ADP Ribose Transferases; C063007:exoenzyme C3, Clostridium botulinum; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D001905:Botulinum Toxins; D020741:rho GTP-Binding Proteins