The Wilms' tumor suppressor Wt1 is associated with the differentiation of retinoblastoma cells.
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.
Wagner
Nicole
N
Johannes-Müller-Institut für Physiologie, Humboldt-Universität, Charité, 10117 Berlin, Germany.
Wagner
Kay-Dietrich
KD
Schley
Gunnar
G
Coupland
Sarah E
SE
Heimann
Heinrich
H
Grantyn
Rosemarie
R
Scholz
Holger
H
D002454:Cell Differentiation / Q000235:genetics*; D002455:Cell Division / Q000235:genetics; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D015536:Down-Regulation / Q000502:physiology*; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D006801:Humans; D007797:Laminin / Q000378:metabolism / Q000494:pharmacology; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D020320:Oligoribonucleotides, Antisense; D012333:RNA, Messenger / Q000378:metabolism; D012160:Retina / Q000378:metabolism* / Q000503:physiopathology; D019572:Retinal Neoplasms / Q000235:genetics / Q000378:metabolism*; D012175:Retinoblastoma / Q000235:genetics / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D025721:WT1 Proteins / Q000235:genetics / Q000378:metabolism*
D007797:Laminin; D020320:Oligoribonucleotides, Antisense; D012333:RNA, Messenger; D025721:WT1 Proteins