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.

[1]  F. Barr.  Molecular Genetics and Pathogenesis of Rhabdomyosarcoma , 1997, Journal of pediatric hematology/oncology.

[2]  R. Davis,et al.  Fusion genes resulting from alternative chromosomal translocations are overexpressed by gene-specific mechanisms in alveolar rhabdomyosarcoma. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[3]  P. Sorensen,et al.  Common and variant gene fusions predict distinct clinical phenotypes in rhabdomyosarcoma. , 1997, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[4]  B. Schäfer,et al.  Induction of apoptosis in rhabdomyosarcoma cells through down-regulation of PAX proteins. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[5]  P. Vogt,et al.  The hybrid PAX3-FKHR fusion protein of alveolar rhabdomyosarcoma transforms fibroblasts in culture. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[6]  F. Barr,et al.  Mechanism for transcriptional gain of function resulting from chromosomal translocation in alveolar rhabdomyosarcoma. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[7]  K. Kelly,et al.  A consensus polymerase chain reaction-oligonucleotide hybridization approach for the detection of chromosomal translocations in pediatric bone and soft tissue sarcomas. , 1995, American journal of clinical pathology.

[8]  P. Gruss,et al.  Pax3: A paired domain gene as a regulator in PNS myelination , 1995, Neuron.

[9]  Carmen Birchmeier,et al.  Essential role for the c-met receptor in the migration of myogenic precursor cells into the limb bud , 1995, Nature.

[10]  J. Epstein,et al.  Pax3 Inhibits Myogenic Differentiation of Cultured Myoblast Cells (*) , 1995, The Journal of Biological Chemistry.

[11]  M. Goulding,et al.  Regulation of Pax-3 expression in the dermomyotome and its role in muscle development. , 1994, Development.

[12]  I. Kawase,et al.  Complementary DNA sequence encoding the major neural cell adhesion molecule isoform in a human small cell lung cancer cell line. , 1994, Lung cancer.

[13]  B. Emanuel,et al.  Fusion of a fork head domain gene to PAX3 in the solid tumour alveolar rhabdomyosarcoma , 1993, Nature Genetics.

[14]  D. Trasler,et al.  N-CAM alterations in splotch neural tube defect mouse embryos. , 1991, Development.

[15]  M. Goulding,et al.  Pax‐3, a novel murine DNA binding protein expressed during early neurogenesis. , 1991, The EMBO journal.

[16]  G M Edelman,et al.  Cell adhesion molecules in the regulation of animal form and tissue pattern. , 1986, Annual review of cell biology.

[17]  J. Epstein,et al.  Pax 3 modulates expression of the c-Met receptor during limb muscle development ( myogenesis / hepatocyte growth factor / embryogenesis / rhabdomyosarcoma / transcriptional regulation ) , 2022 .