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dc.contributor.authorSelga i Coma, Elisabet-
dc.contributor.authorOleaga Sancho, Carlota-
dc.contributor.authorRamírez, Sara-
dc.contributor.authorAlmagro García, Ma. Cristina de-
dc.contributor.authorNoé Mata, Verónica-
dc.contributor.authorCiudad i Gómez, Carlos Julián-
dc.description.abstractBACKGROUND: The need for an integrated view of data obtained from high-throughput technologies gave rise to network analyses. These are especially useful to rationalize how external perturbations propagate through the expression of genes. To address this issue in the case of drug resistance, we constructed biological association networks of genes differentially expressed in cell lines resistant to methotrexate (MTX). METHODS: Seven cell lines representative of different types of cancer, including colon cancer (HT29 and Caco2), breast cancer (MCF-7 and MDA-MB-468), pancreatic cancer (MIA PaCa-2), erythroblastic leukemia (K562) and osteosarcoma (Saos-2), were used. The differential expression pattern between sensitive and MTX-resistant cells was determined by whole human genome microarrays and analyzed with the GeneSpring GX software package. Genes deregulated in common between the different cancer cell lines served to generate biological association networks using the Pathway Architect software. RESULTS: Dikkopf homolog-1 (DKK1) is a highly interconnected node in the network generated with genes in common between the two colon cancer cell lines, and functional validations of this target using small interfering RNAs (siRNAs) showed a chemosensitization toward MTX. Members of the UDP-glucuronosyltransferase 1A (UGT1A) family formed a network of genes differentially expressed in the two breast cancer cell lines. siRNA treatment against UGT1A also showed an increase in MTX sensitivity. Eukaryotic translation elongation factor 1 alpha 1 (EEF1A1) was overexpressed among the pancreatic cancer, leukemia and osteosarcoma cell lines, and siRNA treatment against EEF1A1 produced a chemosensitization toward MTX. CONCLUSIONS: Biological association networks identified DKK1, UGT1As and EEF1A1 as important gene nodes in MTX-resistance. Treatments using siRNA technology against these three genes showed chemosensitization toward MTX.-
dc.format.extent16 p.-
dc.publisherBioMed Central-
dc.relation.isformatofReproducció del document publicat a:
dc.relation.ispartofGenome Medicine, 2009, vol. 1, num. 9, p. 83-
dc.rightscc-by (c) Selga i Coma, Elisabet et al., 2009-
dc.sourceArticles publicats en revistes (Bioquímica i Biomedicina Molecular)-
dc.subject.classificationResistència als medicaments-
dc.subject.classificationCèl·lules canceroses-
dc.subject.classificationQuimioteràpia del càncer-
dc.subject.classificationCicle cel·lular-
dc.subject.otherDrug resistance-
dc.subject.otherCancer cells-
dc.subject.otherCancer chemotherapy-
dc.subject.otherCell cycle-
dc.titleNetworking of differentially expressed genes in human cancer cells resistant to methotrexate-
Appears in Collections:Articles publicats en revistes (Bioquímica i Biomedicina Molecular)

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