Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0035412 (rhabdomyosarcoma)
 6,156 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Two clonal rat rhabdomyosarcoma cell lines BA-Han-1B and BA-Han-1C with different capacities for myogenic differentiation have been examined for the expression of muscle regulatory basic helix-loop-helix (bHLH) proteins of the MyoD family. Whereas cells of the BA-Han-1C subpopulation constitutively expressed MyoD1 and could be induced to differentiate with retinoic acid (RA), BA-Han-1B cells did not express any of the myogenic control factors and appeared to be largely differentiation-defective. Upon induction with RA, BA-Han-1C cells expressed also myogenin, in contrast to BA-Han-1B cells which never activated any of the genes encoding muscle bHLH factors. The onset of myogenin transcription in BA-Han-1C cells required de novo protein synthesis and DNA replication suggesting that RA probably did not act directly on the myogenin gene. Although MyoD1 was expressed in proliferating BA-Han-1C myoblasts, muscle-specific reporter genes were not activated indicating that MyoD was biologically inactive. However, transfections with plasmid expressing additional MyoD1 protein resulted in the transactivation of muscle genes even in the absence of RA. mRNA encoding the negative regulatory HLH protein Id was expressed in proliferating BA-Han-1C cells and disappeared later after RA induction which suggested that it may be involved in the regulation of MyoD1 activity. The myogenic differentiation of malignant rhabdomyosarcoma cells strictly correlated with the activation of the myogenin gene. In fact, stable transfections of BA-Han-1C cells with myogenin expressing plasmids resulted in spontaneous differentiation. Together, our results suggest that the transformed and undifferentiated phenotype of BA-Han-1C rhabdomyosarcoma cells is associated with the inactivation of the myogenic factor MyoD1 as well as lack of myogenin expression. RA alleviates the inhibition of myogenic differentiation, probably by activating MyoD protein and myogenin gene transcription. BA-Han-1B cells did not respond to RA and the differentiated phenotype could not be restored by overexpression of MyoD1 or myogenin.
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PMID:Retinoic acid induces myogenin synthesis and myogenic differentiation in the rat rhabdomyosarcoma cell line BA-Han-1C. 132 66

The myogenic basic helix-loop-helix proteins are essential components of the regulatory network controlling vertebrate myogenesis. However, determined myoblasts appear in the limb buds which do not initially express any member of this transcription factor family. In a search for potential novel regulators of myogenesis, a human PAX-7 cDNA was isolated from primary myoblasts. Analysis of the DNA-binding properties of the Pax-7 paired domain revealed that it binds DNA in a sequence-specific manner indistinguishable from that of the paralogous Pax-3 protein. Each of the two proteins also binds to palindromic homeodomain-binding sites by cooperative dimerization. Both Pax-3 and Pax-7, which are known to partially overlap in their expression during development, can also efficiently form heterodimers on these sites and stimulate reporter gene transcription in transient transfection experiments which, in the case of Pax-7, is dependent on the transactivation function encoded by the C-terminal sequences. Thus, the formation of heterodimers might have important consequences for target gene recognition and regulation during development. PAX-7 was found to be weakly expressed in normal human myoblasts, while PAX-3 could not be detected in these cells at all. However, transcripts for either PAX-3 and/or PAX-7 were expressed at elevated levels in tumorigenic rhabdomyosarcoma cell lines. Hence, overexpression of these PAX genes may be involved in the genesis of myogenic tumors.
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PMID:Molecular cloning and characterization of a human PAX-7 cDNA expressed in normal and neoplastic myocytes. 752 37

The basic helix-loop-helix protein MyoD induces muscle structural gene expression and cell cycle withdrawal in many nontransformed cell lines. We show that MyoD activation of transcription of the cyclin-dependent kinase inhibitor p21 does not require synthesis of an intermediary protein. In most of the rhabdomyosarcoma and other solid tumor cell lines that we analyzed, p21 levels were abnormally low and correlated with the combined inactivity of MyoD and p53, two known transcriptional activators of p21. Loss of MyoD activation of p21 transcription correlated with the failure to arrest in G1, and expression of p21 caused accumulation of cells in G1, further supporting a role for p21 in MyoD-induced cell cycle arrest. Finally, different tumor types have inactivated distinct factors necessary for p21 expression, because p21 expression was reconstituted in hybrid cell lines. We propose that p21 integrates growth-inhibitory signals from independent p53 and basic helix-loop-helix pathways, and that in the majority of tumor cell lines, both pathways are abrogated.
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PMID:Inactivation of MyoD-mediated expression of p21 in tumor cell lines. 937 38

Rhabdomyosarcoma is a pediatric tumor of skeletal muscle that expresses the myogenic basic helix-loop-helix protein MyoD but fails to undergo terminal differentiation. Prior work has determined that DNA binding by MyoD occurs in the tumor cells, but myogenic targets fail to activate. Using MyoD chromatin immunoprecipitation coupled to high-throughput sequencing and gene expression analysis in both primary human muscle cells and RD rhabdomyosarcoma cells, we demonstrate that MyoD binds in a similar genome-wide pattern in both tumor and normal cells but binds poorly at a subset of myogenic genes that fail to activate in the tumor cells. Binding differences are found both across genomic regions and locally at specific sites that are associated with binding motifs for RUNX1, MEF2C, JDP2, and NFIC. These factors are expressed at lower levels in RD cells than muscle cells and rescue myogenesis when expressed in RD cells. MEF2C is located in a genomic region that exhibits poor MyoD binding in RD cells, whereas JDP2 exhibits local DNA hypermethylation in its promoter in both RD cells and primary tumor samples. These results demonstrate that regional and local silencing of differentiation factors contributes to the differentiation defect in rhabdomyosarcomas.
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PMID:Comparison of genome-wide binding of MyoD in normal human myogenic cells and rhabdomyosarcomas identifies regional and local suppression of promyogenic transcription factors. 2323 Feb 69

Rhabdomyosarcoma (RMS) is an aggressive family of soft tissue tumors that most commonly manifests in children. RMS variants express several skeletal muscle markers, suggesting myogenic stem or progenitor cell origin of RMS. In this review, the roles of both recently identified and well-established microRNAs in RMS are discussed and summarized in a succinct, tabulated format. Additionally, the subtypes of RMS are reviewed along with the involvement of basic helix-loop-helix (bHLH) proteins, Pax proteins, and microRNAs in normal and pathologic myogenesis. Finally, the current and potential future treatment options for RMS are outlined.
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PMID:An Examination of the Role of Transcriptional and Posttranscriptional Regulation in Rhabdomyosarcoma. 2863 14