Generation of biological association networks: A novel strategy to detect new targets in cancer therapy
Elisabet Selga i Coma, Ma. Cristina de Almagro García, Carlota Oleaga Sancho, Nuria Mencia Trinchant, Sara Ramírez, Francesc X. Ruiz, Jaume Farrés i Vicèn, Xavier Parés i Casasampera, Rémi Thibaut, Cinta Porte Visa, Verónica Noé Mata, Carlos Julián Ciudad i Gómez · Transworld Research Network eBooks · 2011
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, PKCα, S100A4, DKK1, and CAV1 were overexpressed while E-cadherin was lost. In breast cancer cells, the UGT1A family was overexpressed, whereas EEF1A1 was Correspondence/Reprint request: Dr. Carlos J. Ciudad, Department of Biochemistry and Molecular Biology School of Pharmacy. University of Barcelona, Spain. E-mail: [email protected] Elisabet Selga et al. 2 overexpressed in pancreatic cells. Interference RNAs directed against these targets sensitized cells towards MTX.