title: The Fem1a gene is downregulated in Rhabdomyosarcoma.
abstract: Rhabdomyosarcoma (RMS) is the most common soft tissue neoplasm of children, and those metastatic at presentation have a poor prognosis. RMS development is related to defective skeletal muscle differentiation, involving a variety of cell signaling and transcriptional control pathways, including aberrant hedgehog signaling. Here we evaluate Fem1a, a gene highly expressed in skeletal muscle, as a candidate for involvement in RMS. Fem1a is a homolog of fem-1, which controls cell fate decisions in the sex determination pathway of Caenorhabditis elegans, a pathway with homology to mammalian hedgehog signaling. We show that Fem1a expression is activated during myocyte differentiation of C2C12 myoblasts, and this expression is largely confined to the terminally differentiating pool, not to the satellite-cell-like quiescent reserve cell pool. We find that the human homolog, FEM1A, is downregulated in all of 8 different human RMS cell lines, including those derived from embryonal and alveolar RMS. Using mouse genetic models of RMS development, we further show that Fem1a is consistently downregulated in primary RMS from Ptch1+/- mice, from p53-/- mice, from p53+/-; Ptch1+/- mice, and from HGF/SF-Ink4a/Arf-/- mice. Therefore, Fem1a downregulation may be involved in, and/or a marker of, an early cell fate defect fundamental to RMS pathogenesis.
authors.affiliation: GV (Sonny) Montgomery Veterans Affairs Medical Center, Jackson, MS 39216, USA.
authors.forename: Tereza
authors.initials: T
authors.lastname: Ventura-Holman
authors.forename: Heidi
authors.initials: H
authors.lastname: Hahn
authors.forename: Jose S
authors.initials: JS
authors.lastname: Subauste
authors.forename: Joseph F
authors.initials: JF
authors.lastname: Maher
mesh_terms: D000818:Animals; D018797:Cell Cycle Proteins / Q000235:genetics*; D002454:Cell Differentiation; D015536:Down-Regulation / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D006801:Humans; D051379:Mice; D032342:Muscle Cells / Q000166:cytology / Q000378:metabolism; D009132:Muscles / Q000378:metabolism; D012208:Rhabdomyosarcoma / Q000145:classification / Q000235:genetics*; D014407:Tumor Cells, Cultured
chemical_list: D018797:Cell Cycle Proteins; C444344:FEM1A protein, human; C506176:Fem1a protein, mouse