Up-regulation of MET but not neural cell adhesion molecule expression by the PAX3-FKHR fusion protein in alveolar rhabdomyosarcoma.
The 2;13 chromosomal translocation in alveolar rhabdomyosarcoma generates the chimeric protein PAX3-FKHR, which is a powerful transcriptional activator. We hypothesize that PAX3-FKHR regulates downstream effector genes involved in rhabdomyosarcoma tumorigenesis. We evaluated alterations in expression of MET and neural cell adhesion molecule that were proposed previously as downstream targets of wild-type PAX3. We used a myogenic tumor cell culture system and rhabdomyosarcoma tumor specimens to assess candidate gene expression in relationship to various PAX3-FKHR expression levels. We demonstrate that the expression of MET, but not neural cell adhesion molecule, correlates significantly with PAX3-FKHR expression. These findings indicate that MET, which encodes a receptor involved in growth and motility signaling, is a downstream target of PAX3-FKHR in alveolar rhabdomyosarcoma.
Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia 19104-6082, USA.
J P
JP
Ginsberg
R J
RJ
Davis
J L
JL
Bennicelli
L E
LE
Nauta
F G
FG
Barr
D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology*; D006801:Humans; D009363:Neoplasm Proteins / Q000378:metabolism*; D019006:Neural Cell Adhesion Molecules / Q000378:metabolism*; D019859:Proto-Oncogene Proteins c-met / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000502:physiology*; D018232:Rhabdomyosarcoma, Alveolar / Q000378:metabolism*; D015533:Transcriptional Activation; D014162:Transfection; D014407:Tumor Cells, Cultured; D015854:Up-Regulation
D004268:DNA-Binding Proteins; D009363:Neoplasm Proteins; D019006:Neural Cell Adhesion Molecules; D011993:Recombinant Fusion Proteins; D019859:Proto-Oncogene Proteins c-met