WT1 expression alters tumorigenicity of the G401 kidney-derived cell line.
Recent studies have implicated a loss of WT1 tumor suppressor gene function in the development of Wilms' tumor (WT). To determine the potential biological consequences of WT1 inactivation in these tumors, we transfected two different splice variant forms of this gene into the pediatric kidney-derived cell line G401. Introduction of this gene caused no detectable effects on the population doubling times of the cell line; proliferative capacity in soft agar was not significantly affected. However, the expression of this gene altered the morphology of the cells in culture and caused a significant suppression of tumorigenicity in the cells. Thus, the expression of WT1 in a pediatric kidney-derived cell line lacking endogenous WT1 production caused demonstrable effects on its in vitro and in vivo growth properties. These data strengthen the concept for a central role for WT1 inactivation in the etiology of this disease.
McMaster
M L
ML
Department of Pathology, University of North Carolina, Chapel Hill 27599, USA.
Gessler
M
M
Stanbridge
E J
EJ
Weissman
B E
BE
D000818:Animals; D001483:Base Sequence; D015152:Blotting, Northern; D002455:Cell Division; D002460:Cell Line; D002471:Cell Transformation, Neoplastic; D002880:Chromosomes, Human, Pair 11; D017931:DNA Primers; D004268:DNA-Binding Proteins / Q000096:biosynthesis*; D005260:Female; D016162:Genes, Wilms Tumor; D006801:Humans; D007335:Insulin-Like Growth Factor II / Q000096:biosynthesis; D007668:Kidney; D007680:Kidney Neoplasms / Q000235:genetics*; D051379:Mice; D008819:Mice, Nude; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D011994:Recombinant Proteins / Q000096:biosynthesis; D014157:Transcription Factors / Q000096:biosynthesis*; D014162:Transfection; D014183:Transplantation, Heterologous; D025721:WT1 Proteins; D009396:Wilms Tumor / Q000235:genetics*
D017931:DNA Primers; D004268:DNA-Binding Proteins; D011994:Recombinant Proteins; D014157:Transcription Factors; D025721:WT1 Proteins; D007335:Insulin-Like Growth Factor II