WT1 expression does not disrupt myogenic differentiation in C2C12 murine myoblasts or in human rhabdomyosarcoma.
WT1 encodes a tissue-specific transcription factor important in early mesenchymal differentiation. Altered expression or mutation of WT1 occurs in malignancies derived from such tissues. These include Wilms tumour, a paediatric kidney cancer that may show heterologous differentiation into primitive skeletal muscle, especially in tumours with WT1 mutation. A putative role for WT1 in inhibiting myogenesis has been suggested by transient transfection of C(2)C(12) myoblasts. However, using a more robust model of stable transfectants of C(2)C(12) expressing inducible WT1 isoforms, we found no inhibition of myogenic differentiation. We also investigated a possible role for WT1 in the disrupted myogenesis seen in rhabdomyosarcoma, a paediatric cancer resembling foetal skeletal muscle. WT1 expression levels measured by quantitative real-time reverse transcription polymerase chain reaction were low or absent in those tumours with a PAX-FKHR fusion gene characteristic of the alveolar subtype, and were higher in cases lacking these fusion genes. Overall, there was a weak positive correlation between expression of myogenic differentiation marker genes and WT1 levels. We conclude that expression of WT1 in C(2)C(12) cells and in rhabdomyosarcoma does not inhibit myogenic differentiation.
Tiffin
Nicki
N
Section of Paediatric Oncology, Institute of Cancer Research, 15 Cotswold Road, Belmont, Sutton, SM2 5NG, Surrey, UK.
Williams
Richard D
RD
Robertson
David
D
Hill
Suzanne
S
Shipley
Janet
J
Pritchard-Jones
Kathy
K
D000818:Animals; D002454:Cell Differentiation / Q000235:genetics*; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D006801:Humans; D008648:Mesoderm / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D018482:Muscle, Skeletal / Q000166:cytology / Q000196:embryology* / Q000378:metabolism; D032446:Myoblasts / Q000166:cytology / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics; D012208:Rhabdomyosarcoma / Q000235:genetics* / Q000378:metabolism; D025721:WT1 Proteins / Q000235:genetics* / Q000378:metabolism
D012333:RNA, Messenger; D011993:Recombinant Fusion Proteins; D025721:WT1 Proteins