Abstract 335: Human neuroblastoma cells undergo TGF-beta mediated mesenchymal change in the transition to drug resistance

Background: Hypoxia inducible factor 1-alpha (HIF1-alpha) is overexpressed in doxorubicin-resistant neuroblastoma cell lines relative to drug sensitive parental cells lines, and has been implicated in inducing epithelial to mesenchymal transition (EMT). We hypothesized that the transition of human neuroblastoma cells from a drug-sensitive to drug-resistant phenotype involves mesenchymal change. Methods: A doxorubicin resistant (DoxR) human neuroblastoma cell line was generated by incubating parental wild type (WT) SK-N-Be(2)C cells in stepwise concentrations of doxorubicin. Cells were deemed resistant after surviving in a concentration of drug approximately 2 Log above the wild type IC50, confirmed by MTT colorimetric survival assay. Cell migration and capacity for invasion were assayed using the scratch test and Matrigel invasion culture system. EMT pathway related genes differentially expressed in the DoxR cells relative to the parental (WT) lines were analyzed using the Ilumina Human HT-12 v4 Expression Beadchip. Genes of interest with a fold change in expression >1.5 and an adjusted p Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 335. doi:1538-7445.AM2012-335