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PAX3-NCOA2 fusion gene has a dual role in promoting the proliferation and inhibiting the myogenic differentiation of rhabdomyosarcoma cells


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.

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alveolar rhabdomyosarcoma


bacterial artificial chromosome


sequence similarity with basic helix–loop–helix motifs


CREB-binding protein


complementary DNA


CBP interaction domain


cAMP (cyclic adenosine monophosphate) response element-binding protein


differentiation medium


embryonal rhabdomyosarcoma


fluorescence in situ hybridization


forkhead in human rhabdomyosarcoma


forkhead box O1A




green fluorescent protein


hematoxylin and eosin


LXXLL-containing helical motif


myosin heavy chain


murine stem cell virus


nuclear receptor coactivator 2


nuclear receptor-interacting domain


sequence similarity with the Per Arndt-Sim (PAS) motifs


paired box 3


phosphate-buffered saline


phosphate-buffered saline with Tween 20


propidium iodide




reverse transcription–polymerase chain reaction


sodium dodecylsulfate–polyacrylamidegel electrophoresis


transactivation domain


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This work was supported by Grant-in-aid for Scientific Research (A) 21249085, (A) 25253095, (B) 22390239, (C) 22591166, Grant-in-aid for Young Scientists (B) 24791078 and Grant-in-aid for Project for Development of Innovative Research on Cancer Therapeutics from the Ministry of Education, Culture, Sports, Science and Technology of Japan.

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Correspondence to H Hosoi.

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Yoshida, H., Miyachi, M., Sakamoto, K. et al. PAX3-NCOA2 fusion gene has a dual role in promoting the proliferation and inhibiting the myogenic differentiation of rhabdomyosarcoma cells. Oncogene 33, 5601–5608 (2014).

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  • rhabdomyosarcoma
  • PAX3-NCOA2
  • tumorigenesis
  • inhibiting differentiation

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