title: The Expression of c-Myb Correlates with the Levels of Rhabdomyosarcoma-specific Marker Myogenin.
abstract: The transcription factor c-Myb is required for modulation of progenitor cells in several tissues, including skeletal muscle and its upregulation is observed in many human malignancies. Rhabdomyosarcomas (RMS) are a heterogeneous group of mesodermal tumors with features of developing skeletal muscle. Several miRNAs are downregulated in RMS, including miR-150, a negative regulator of c-Myb expression. Using the C2C12 myoblast cell line, a cellular model of skeletal muscle differentiation, we showed that miR-150 controls c-Myb expression mainly at the level of translation. We hypothesized that a similar mechanism of c-Myb regulation operates in RMS tumors. We examined expression of c-Myb by immunohistochemistry and revealed c-Myb positivity in alveolar and embryonal tumors, the two most common subgroups of RMS. Furthermore, we showed direct correlation between c-Myb production and myogenin expression. Interestingly, high myogenin levels indicate poor prognosis in RMS patients. c-Myb could, therefore, contribute to the tumor phenotype by executing its inhibitory role in skeletal muscle differentiation. We also showed that c-Myb protein is abundant in migratory C2C12 myoblasts and its ectopic expression potentiates cell motility. In summary, our results implicate that metastatic properties of some RMS subtypes might be linked to c-Myb function.
authors.affiliation: Laboratory of Transgenic Models of Diseases, Institute of Molecular Genetics of the ASCR, v.v.i., Prague, Czech Republic.
authors.forename: Petr
authors.initials: P
authors.lastname: Kaspar
authors.affiliation: Laboratory of Cell Differentiation, Institute of Molecular Genetics of the ASCR, v.v.i., Prague, Czech Republic.
authors.forename: Martina
authors.initials: M
authors.lastname: Zikova
authors.affiliation: Laboratory of Cell Differentiation, Institute of Molecular Genetics of the ASCR, v.v.i., Prague, Czech Republic.
authors.forename: Petr
authors.initials: P
authors.lastname: Bartunek
authors.affiliation: The University Hospital Brno, Brno, Czech Republic.
authors.forename: Jaroslav
authors.initials: J
authors.lastname: Sterba
authors.affiliation: Laboratory of Genomics and Bioinformatics, Institute of Molecular Genetics of the ASCR, v.v.i., Prague, Czech Republic.
authors.forename: Hynek
authors.initials: H
authors.lastname: Strnad
authors.affiliation: The University Hospital Brno, Brno, Czech Republic.
authors.forename: Leos
authors.initials: L
authors.lastname: Kren
authors.affiliation: Laboratory of Transgenic Models of Diseases, Institute of Molecular Genetics of the ASCR, v.v.i., Prague, Czech Republic.
authors.forename: Radislav
authors.initials: R
authors.lastname: Sedlacek
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor / Q000378:metabolism*; D045744:Cell Line, Tumor; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051379:Mice; D018008:Myogenin; D020598:Proto-Oncogene Proteins c-myb / Q000378:metabolism*; D012208:Rhabdomyosarcoma / Q000378:metabolism* / Q000473:pathology / Q000556:secondary*
chemical_list: D014408:Biomarkers, Tumor; D018008:Myogenin; D020598:Proto-Oncogene Proteins c-myb