title: PAX3-NCOA2 fusion gene has a dual role in promoting the proliferation and inhibiting the myogenic differentiation of rhabdomyosarcoma cells.
abstract: We analyzed a complex chromosomal translocation in a case of embryonal rhabdomyosarcoma (RMS) and showed that it generates the fusion gene PAX3 (paired box 3)-NCOA2 (nuclear receptor coactivator 2). To understand the role of this translocation in RMS tumorigenesis, we established two types of stable mouse myoblast C2C12 cell lines expressing PAX3-NCOA2 and PAX3-FOXO1A (forkhead box O1A), respectively. Compared with control cells, PAX3-NCOA2 cells grew faster, were more motile, were less anchorage dependent, progressed more quickly through the G1/S phase of cell cycle and showed greater transcriptional activation of the PAX3 consensus-binding site. However, PAX3-NCOA2 cells proliferated more slowly and differentiated more weakly than did PAX3-FOXO1A cells. Both PAX3-NCOA2 cells and PAX3-FOXO1A cells formed tumors in nude mice, although the PAX3-NCOA2-induced tumors grew more slowly. Our results may explain why NCOA2 rearrangement is mainly found in embryonal rhabdomyosarcoma, which has a better prognosis than alveolar rhabdomyosarcoma, which expresses the PAX3-FOXO1A fusion gene. These results indicate that the PAX3-NCOA2 fusion gene has a dual role in the tumorigenesis of RMS: promotion of the proliferation and inhibition of the myogenic differentiation of RMS cells.
authors.affiliation: Department of Pediatrics, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Yoshida
authors.affiliation: Department of Pediatrics, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Miyachi
authors.affiliation: Department of Pediatrics, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Sakamoto
authors.affiliation: Department of Pediatrics, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Ouchi
authors.affiliation: Department of Pediatrics, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Yagyu
authors.affiliation: Department of Pediatrics, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Kikuchi
authors.affiliation: Department of Pediatrics, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Kuwahara
authors.affiliation: Department of Pediatrics, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Tsuchiya
authors.affiliation: Department of Pediatrics, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Imamura
authors.affiliation: Department of Pediatrics, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Iehara
authors.affiliation: Department of Environmental and Preventive Medicine, Shimane University School of Medicine, Shimane, Japan.
authors.forename: N
authors.initials: N
authors.lastname: Kakazu
authors.affiliation: First Department of Pathology, Fukushima Medical University School of Medicine, Fukushima, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Hojo
authors.affiliation: Department of Pediatrics, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Hosoi
mesh_terms: D000818:Animals; D001665:Binding Sites; D002453:Cell Cycle; D002454:Cell Differentiation; D002460:Cell Line; D002465:Cell Movement; D049109:Cell Proliferation; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors / Q000378:metabolism; D017353:Gene Deletion; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D024510:Muscle Development; D009154:Mutation; D051958:Nuclear Receptor Coactivator 2 / Q000378:metabolism*; D050596:Oncogene Fusion; D000072041:PAX3 Transcription Factor; D051761:Paired Box Transcription Factors / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012208:Rhabdomyosarcoma / Q000235:genetics*; D015533:Transcriptional Activation; D014178:Translocation, Genetic; D014945:Wound Healing
chemical_list: D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors; C467200:Foxo1 protein, mouse; C498001:NCOA2 protein, human; C498002:Ncoa2 protein, mouse; D051958:Nuclear Receptor Coactivator 2; D000072041:PAX3 Transcription Factor; C489409:PAX3 protein, human; D051761:Paired Box Transcription Factors; C068686:Pax3 protein, mouse