The oncogenic LIM protein Rbtn2 causes thymic developmental aberrations that precede malignancy in transgenic mice.
RBTN2 is activated by the chromosomal translocation t(11;14) (P13;p11) in some T cell leukaemias. Histologically similar T cell tumours develop with long latency in transgenic mice when either CD2 or thy1.1 promoters control rbtn2 expression. During the asymptomatic period, perturbation of T cell differentiation occurs in the thymus. The major anomalies present during this phase are an increase in the percentage of large thymocytes lacking CD4 and CD8 markers and also of small thymocytes express both the T cell marker CD3 and the B cell-specific form of CD45. These abnormal T cell populations can be clonal and thus a primary result of aberrant expression of the LIM-protein Rbtn2 is alteration of T cell differentiation preceding overt malignancy. These data provide a biological explanation for the role of Rbtn2 in tumorigenesis and presumably RBTN2 expression in T cells after the translocation t(11;14) in children has the same effect.
Larson
R C
RC
MRC Laboratory of Molecular Biology, Cambridge, UK.
Osada
H
H
Larson
T A
TA
Lavenir
I
I
Rabbitts
T H
TH
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D000954:Antigens, Surface / Q000032:analysis; D018801:CD2 Antigens / Q000502:physiology; D017252:CD3 Complex / Q000032:analysis; D015704:CD4 Antigens / Q000032:analysis; D016827:CD8 Antigens / Q000032:analysis; D002454:Cell Differentiation; D004268:DNA-Binding Proteins / Q000502:physiology*; D060588:LIM Domain Proteins; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000209:etiology*; D017493:Leukocyte Common Antigens; D008667:Metalloproteins / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic; D011518:Proto-Oncogene Proteins / Q000502:physiology*; D013601:T-Lymphocytes / Q000276:immunology*; D014178:Translocation, Genetic
D048868:Adaptor Proteins, Signal Transducing; D000954:Antigens, Surface; D018801:CD2 Antigens; D017252:CD3 Complex; D015704:CD4 Antigens; D016827:CD8 Antigens; D004268:DNA-Binding Proteins; D060588:LIM Domain Proteins; C513188:Lmo2 protein, mouse; D008667:Metalloproteins; D011518:Proto-Oncogene Proteins; D017493:Leukocyte Common Antigens