Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Expression data from Docetaxel-resistant prostate cancer cells

ABSTRACT: Docetaxel is the standard first line therapy for hormone-refractory prostate cancer patients. Here we generated models of Docetaxel resistance in prostate cancer cells to study the molecular pathways that drive the acquisition of resistance to this therapy. We used microarrays to detail the global program of gene expression underlying the acquisition of Docetaxel resistance in prostate cancer cells. Parental Docetaxel-sensitive prostate cancer cell lines (DU145 and 22Rv1) and selected Docetaxel-resistant cells (DU145-DR and 22Rv1-DR) were harvested for RNA extraction and hybridization on Affymetrix microarrays. Samples were analyzed in triplicates in order to increase the resolution of expression profiles.

ORGANISM(S): Homo sapiens

SUBMITTER: Josep Domingo-Domenech

PROVIDER: E-GEOD-36135 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Suppression of acquired docetaxel resistance in prostate cancer through depletion of notch- and hedgehog-dependent tumor-initiating cells.

Domingo-Domenech Josep J Vidal Samuel J SJ Rodriguez-Bravo Veronica V Castillo-Martin Mireia M Quinn S Aidan SA Rodriguez-Barrueco Ruth R Bonal Dennis M DM Charytonowicz Elizabeth E Gladoun Nataliya N de la Iglesia-Vicente Janis J Petrylak Daniel P DP Benson Mitchell C MC Silva Jose M JM Cordon-Cardo Carlos C

Cancer cell 20120901 3

Acquired resistance to Docetaxel precedes fatality in hormone-refractory prostate cancer (HRPC). However, strategies that target Docetaxel resistant cells remain elusive. Using in vitro and in vivo models, we identified a subpopulation of cells that survive Docetaxel exposure. This subpopulation lacks differentiation markers and HLA class I (HLAI) antigens, while overexpressing the Notch and Hedgehog signaling pathways. These cells were found in prostate cancer tissues and were related to tumor ...[more]

PMID: 22975379

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Project description:Background: Current protocols for the treatment of ovarian cancer include combination chemotherapy with a platinating agent and a taxane. However, many patients experience relapse of their cancer and the development of drug resistance is not uncommon, making successful second line therapy difficult to achieve. The objective of this study was to develop a cell line resistant to both carboplatin and docetaxel (dual drug resistant ovarian cell line A2780CBNDXL), along with single agent resistant lines (docetaxel resistant A2780DXL and carboplatin resistant A2780CBN), to investigate the mechanisms which underlie the development of dual drug resistance. Methods: The A2780 epithelial ovarian cancer cell line was used to select for isogenic carboplatin, docetaxel and dual drug resistant cell lines. A selection method of gradually increasing drug doses was implemented to avoid clonal selection. Resistance was confirmed using a clonogenic assay. Changes in gene expression associated with the development of drug resistance were determined by microarray analysis compared to parental co-culture control A2780CC. Changes in selected genes were validated by QPCR and immunoblotting. Results: Three isogenic cell lines were developed and resistance to each drug or the combination of drugs was confirmed. Development of resistance was accompanied by a reduced growth rate. The microarray and QPCR analyses showed that unique changes in gene expression occurred in the dual drug resistant cell line and that genes known to be involved in resistance could be identified in all cell lines. Conclusions: Novel changes in gene expression can occur in the development of dual drug resistance, indicating that dual drug resistance is not a simple combination of the changes occurring in single agent resistance Carboplatin, docetaxel (GSE26129) and carboplatin/docetaxel dual resistant cell lines of ovarian A2780 were generated for gene expression profilling. Two colour microarray of Agilent whole human genome nucleotide arrays was conducted with two replicate of both forward and reverse labellings for each cell line. Four arrays were used for this experiments. And it was four replicate of both forward and reverse labellings for A2780 cells. Eight arrays were used for this experiments

Dataset Information

Expression data from Docetaxel-resistant prostate cancer cells

Publications

Suppression of acquired docetaxel resistance in prostate cancer through depletion of notch- and hedgehog-dependent tumor-initiating cells.

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