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The Wilms’ Tumor Suppressor Wt1 Is Associated with the Differentiation of Retinoblastoma Cells¹

Johannes-Müller-Institut für Physiologie, Humboldt-Universität, Charité, 10117 Berlin [N. W., K. D. W., G. S., R. G., H. S.]; Medizinische Klinik I, Humboldt-Universität, Charité, 10117 Berlin [N. W.]; and Institut für Pathologie [S. E. C.] and Klinik für Ophthalmologie [H. H.], Universitätsklinikum Benjamin Franklin, Freie Universität Berlin, 12200 Berlin, Germany

We have demonstrated recently that Wilms’ tumor suppressor 1 (Wt1),in addition to its role in genitourinary formation,is required for the differentiation of ganglion cells in the developing retina. Here we provide further evidence that Wt1 is associated with neuronal differentiation. Thus, the retinoblastoma-derived human cell line, Y-79, contained robust amounts of Wt1 mRNA and protein. Wt1 expression was down-regulated upon laminin-induced differentiation of Y-79 into neuron-like cells. Inhibition of Wt1 with antisense oligonucleotides dramatically reduced the capacity of undifferentiated Y-79 cells to undergo neuronal differentiation, whereas sense and missense oligonucleotides had no effect. Wt1 immunoreactivity was also detected in solid retinoblastomas, in which it resided mainly in areas with moderate proliferative activity. These findings suggest a role for Wt1 in the differentiation of retinoblastoma cells. Furthermore, Wt1 expression in retinoblastoma may reflect the potential of these tumors to initiate the early steps of neuronal differentiation.

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