551. Generation of biological association networks: A novel strategy to detect new targets in cancer therapy
- Author
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Selga i Coma, Elisabet, Almagro García, Ma. Cristina de, Oleaga Sancho, Carlota, Mencía Trinchant, Núria, Ramírez, Sara, Ruiz, F. Xavier, Farrés i Vicén, Jaume, Parés i Casasampera, Xavier, Thibaut, Rémi, Porte Visa, Cinta, Noé Mata, Verónica, Ciudad i Gómez, Carlos Julián, and Universitat de Barcelona
- Subjects
InformationSystems_GENERAL ,Pharmacogenetics ,Quimioteràpia ,Farmacogenètica ,Chemotherapy ,Càncer ,GeneralLiterature_REFERENCE(e.g.,dictionaries,encyclopedias,glossaries) ,Cancer - Abstract
Podeu consultar el llibre complet a: http://www.trnres.com/ebookcontents.php?id=149, The aim of this work was to design a novel strategy to detect new targets for anticancer treatments. The rationale was to build Biological Association Networks from differentially expressed genes in drug-resistant cells to identify important nodes within the Networks. These nodes may represent putative targets to attack in cancer therapy, as a way to destabilize the gene network developed by the resistant cells to escape from the drug pressure. As a model we used cells resistant to methotrexate (MTX), an inhibitor of DHFR. Selected node-genes were analyzed at the transcriptional level and from a genotypic point of view. In colon cancer cells, DHFR, the AKR1 family, PKC¿, S100A4, DKK1, and CAV1 were overexpressed while E-cadherin was lost. In breast cancer cells, the UGT1A family was overexpressed, whereas EEF1A1 was overexpressed in pancreatic cells. Interference RNAs directed against these targets sensitized cells towards MTX.