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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2011-2-17
pubmed:abstractText
Expression profiling of tumor tissue allows a systematic search for targeted therapies and offers relevant prognostic information. Molecular studies on rhabdomyosarcoma (RMS) revealed a more differentiated classification than the histological subgrouping into embryonal (RME) and alveolar (RMA) rhabdomyosarcoma, and reflected the chromosomal aberrations found in RMS. We addressed biological processes like cell migration and emerging drug resistance by expression profiling to identify mechanisms of metastasic invasion and differential response to chemotherapy in RMS. Gene expression analysis was performed in 19 RMS samples using the Affymetrix U133 Plus2 array. Validation of target genes was performed by qRT-PCR. Data were analyzed using Pathway analysis software. Involvement of these genes in invasion processes was evaluated in knock-down experiments using specific interference RNA and Matrigel(TM) invasion assay. In RMA tissues 211 of 534 genes were overexpressed, in RME tissues 323 genes were overexpressed. Pathway analysis software identified a group of genes involved in cell growth, morphology and motility. In patients with distant metastases especially transcription factors such as FOXF1 and LMO4 showed a high expression, which were described as determinants of tumor cell migration. Down-regulation of these factors inhibited the invasion of RMS cells >10-fold. Microarray technology is a powerful method not only to classify RMS samples, but also to identify major regulatory processes. Functional evaluation of LMO4 and FOXF1 identified targets of a molecular network for preventing metastatic invasion in RMS.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
1791-2423
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
38
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
993-1000
pubmed:dateRevised
2011-11-17
pubmed:meshHeading
pubmed-meshheading:21271214-Adaptor Proteins, Signal Transducing, pubmed-meshheading:21271214-Adolescent, pubmed-meshheading:21271214-Cell Movement, pubmed-meshheading:21271214-Child, pubmed-meshheading:21271214-Child, Preschool, pubmed-meshheading:21271214-Forkhead Transcription Factors, pubmed-meshheading:21271214-Gene Expression Profiling, pubmed-meshheading:21271214-Gene Expression Regulation, Neoplastic, pubmed-meshheading:21271214-Homeodomain Proteins, pubmed-meshheading:21271214-Humans, pubmed-meshheading:21271214-Infant, pubmed-meshheading:21271214-Infant, Newborn, pubmed-meshheading:21271214-LIM Domain Proteins, pubmed-meshheading:21271214-Male, pubmed-meshheading:21271214-Neoplasm Invasiveness, pubmed-meshheading:21271214-Neoplasm Metastasis, pubmed-meshheading:21271214-RNA Interference, pubmed-meshheading:21271214-Rhabdomyosarcoma, Alveolar, pubmed-meshheading:21271214-Rhabdomyosarcoma, Embryonal, pubmed-meshheading:21271214-Transcription Factors, pubmed-meshheading:21271214-Tumor Cells, Cultured
pubmed:year
2011
pubmed:articleTitle
Differential expression of invasion promoting genes in childhood rhabdomyosarcoma.
pubmed:affiliation
Department of Pediatric Surgery, University Children's Hospital, Hoppe-Seyler-Strasse 1, 72076 Tübingen, Germany. sorin.armeanu-ebinger@med.uni-tuebingen.de
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't