Abstract 2019: Molecular pathways involved in docetaxel (D)-resistance hormone-independent prostate cancer (HIPC) cells

Abstract

Abstract Background: D-based chemotherapy is the standard therapy of metastatic HIPC. However, only approximately 50% of patients respond to this treatment and most of them eventually develop resistance to the therapy. The molecular events that lead to D-resistance in HIPC are not well established. Objectives: To determine the main molecular pathways responsible for D-resistance in two different HIPC cells lines. Methodology: DU-145 and PC3 cell lines were converted to D-resistant cells (DU-145R and PC3R, respectively) by means of exposing parental cells to increasing doses of D. Affymetrix U133 Plus 2.0 whole genome arrays were used to compare global gene expression between these four cell lines. Genes, pathways and networks, commonly deregulated in both DU-145R and PC3R cells respect their parental cell lines, were analyzed in detail. Changes in expression of a subset of genes were confirmed by real-time RT-PCR. Results: Differential expression of 321 genes (P<0.05 Bonferroni corrected and logFC>1.2) was found to be common in DU-145R and PC3R cells. Pathway and network analysis showed that these genes were particularly involved in cellular growth and proliferation, gene expression, cellular movement, cellular development, cell death and cell cycle. Other related functions are infection mechanism, cellular assembly and organization, tissue morphology, antigen presentation and cell-mediated immune response. RT-PCR confirmed differential expression in genes related with epithelial-mesenquimal transition (e-CADHERIN, α-CATENIN, VIMENTIN, SNAIL and TWIST), NFkB related genes (IL-6, IL-8, c-REL, P50 and P65) and ErbB signalling pathway family genes (EGFR and HER3). Conclusions: These data reveals a set of gene networks involved in HIPC D-resistance. Key genes from these networks should be investigated further as new targets for potential therapeutic development. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2019.