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)

Many cancer cells show aberrant adhesion properties that likely contribute to tumorigenesis, invasion, and metastasis. Here, we examine three MyoD-expressing, rhabdomyosarcoma-derived human cell lines (RD, A-204, and HS 729) for their expression of the neural cell adhesion molecule (N-CAM), N-cadherin, and the cadherin-associated proteins, alpha-catenin, beta-catenin, and plakoglobin, using specific antibodies and immunoblotting and immunocytochemical methods. Normally, during the formation of skeletal muscle, both N-CAM and N-cadherin are expressed and participate in mediating myoblast adhesion accompanying cell fusion. RD cells express N-CAM, N-cadherin, and the cadherin-associated proteins; however, N-CAM is expressed as a highly sialylated isoform that functions poorly in promoting Ca(2+)-independent cell aggregation. HS 729 cells express N-cadherin and its associated intracellular proteins but have no detectable N-CAM. A-204 cells express no detectable N-CAM or N-cadherin but do express cadherin-associated proteins. Thus, all three rhabdomyosarcoma cell lines exhibit some abnormality in the expression of adhesion molecules known to participate in skeletal myogenesis; however, no common defect was observed that might be considered as a characteristic marker for rhabdomyosarcomas.
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PMID:Rhabdomyosarcoma-derived cell lines exhibit aberrant expression of the cell-cell adhesion molecules N-CAM, N-cadherin, and cadherin-associated proteins. 839 2

The zinc finger transcription factor GLI1, which mediates Sonic hedgehog signaling during development, is expressed in several human cancers, including basal cell carcinoma, medulloblastoma, and sarcomas. We identified 147 genes whose levels of expression were significantly altered in RNA obtained from cells demonstrating a transformed phenotype with stable GLI1 expression or stable Ha-ras expression. Comparison of expression profiles from GLI1- and Ha-ras-expressing cells established a set of genes unique to GLI1-induced cell transformation. Thirty genes were altered by stable GLI1 expression, and 124 genes were changed by stable Ha-ras expression. Seven genes had altered expression levels in both GLI1- and Ha-ras-expressing cells. Genes whose expression was altered by GLI1 included cell cycle genes, cell adhesion genes, signal transduction genes, and genes regulating apoptosis. GLI1 consensus DNA-binding sequences were identified in the 5' regions of cyclin D2, IGFBP-6, osteopontin, and plakoglobin, suggesting that these genes represent immediate downstream targets. Gel shift analysis confirmed the ability of the GLI1 protein to bind these sequences. Up-regulation of cyclin D2 and down-regulation of plakoglobin were demonstrated in GLI1-amplified compared with non-amplified human rhabdomyosarcoma cells. Many of the GLI1 targets with known function identified in this study increase cell proliferation, indicating that GLI1-induced cell transformation occurs through multiple downstream pathways.
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PMID:Gene expression profiling leads to identification of GLI1-binding elements in target genes and a role for multiple downstream pathways in GLI1-induced cell transformation. 1171 6

Plakoglobin (gamma-catenin) and beta-catenin are pivotal components of cell-cell adherent junctions that link cadherin receptors to the actin cytoskeleton. Whereas beta-catenin overexpression induces cell proliferation and tumor formation, plakoglobin induces tumor suppressor activity. We investigated the expression of plakoglobin in alveolar (ARMS) and embryonal (ERMS) rhabdomyosarcoma (RMS) cell lines and tumors, and found that plakoglobin is present both in the cytoplasm and in the nucleus of ERMS cells, whereas it is absent or detectable at extremely low levels in ARMS. As gene silencing can be mediated by methylation and/or deacetylation of promoter regions, we assessed the effects of the DNA demethylating agent 5-Aza-2'-deoxycytidine (5AzadC) and of the histone deacetylase inhibitor Trichostatin A (TSA), and obtained restoration of plakoglobin expression in ARMS cells cultivated in the presence of 5AzadC and TSA. By methylation-specific PCR, ARMS cells were shown to contain methylated CpG dinucleotides in CpG islands located around the transcriptional start site of one or both alleles, whereas ERMS cells did not. Furthermore, we demonstrated that promoter regions (P1-P3) of plakoglobin gene were associated with hypoacetylated H4 histone in ARMS cells RH4, suggesting that aberrant DNA methylation of the 5' CpG island and histone deacetylation play key roles in silencing the plakoglobin gene. These results demonstrate that plakoglobin is differentially expressed in ARMS and ERMS and that its expression depends on the methylation and acetylation status of the gene.
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PMID:Plakoglobin is differentially expressed in alveolar and embryonal rhabdomyosarcoma and is regulated by DNA methylation and histone acetylation. 1653 59