Transcriptomics

Dataset Information

33

Transcription profiling of IGR-CaP1 prostate cancer cells resistant to docetaxel compared to non-resistant cells


ABSTRACT: 'Prostate cancer is the second cancer diagnosed among men worldwide. Beside approval of new therapies in the last five years, chemotherapeutic agents, docetaxel and cabazitaxel taxanes remain key treatments for metastatic castration resistant prostate cancers. However, primary and acquired resistance to taxanes still emerged in about half of patients. There is therefore an urgent need to discover and understand the taxane resistance mechanisms in order to identify new therapeutic targets. Indeed, targeted therapies that exploit the signaling pathways involved in prostate cancer are required to overcome chemoresistance and improve treatment outcomes. Molecular chaperones play a key role in the regulation of cellular homeostasis and the development of treatment resistance, and are promising therapeutic targets. Using high throughput siRNA functional screening based on a gene expression signature, we identified FKBP7, involved in acquired resistance to docetaxel and cabazitaxel. FKBP7 is a molecular chaperone that has not been studied in human so far. FKBP7 is overexpressed in prostate tumors and its expression is correlated with recurrence in patients who received docetaxel as neoadjuvant therapy. Moreover, FKBP7 is upregulated in taxane resistant prostate cancer cell lines and its expression sustains their growth in vitro and in a mice model of Docetaxel resistance. Using a high throughput proteomic approach, we identified the signaling pathway regulated by FKBP7 which is responsible for the survival of chemoresistant cells. Finally, we proposed a promising therapeutic strategy to overcome both docetaxel and cabazitaxel chemoresistance by targeting the downstream effector of FKBP7. Gene expression was profiled using a 4×44K Human Whole Genome (G4112F, id : 014850) expression array (Agilent Technologies, Santa Clara, Cal.) with a dual color dye-swap competitive hybridization procedure, according to the manufacturer''s instructions. Total RNA from untreated parental IGR-CaP1 cells was used as the RNA reference (NN1). Total RNA from IGR-CaP1 cells resistant to 5nM (NN2), 11.6nM (NN3), 25nM (NN4), 50nM (NN5), 100nM (NN6), and 200nM (NN7) of Docetaxel respectively, were used as samples. Two independent replicates of each samples (a and b) were used. Image analyses (quantification, normalization) were performed with Feature Extraction software (Agilent Technologies) and gene expression analysis was performed using Bioconductor.'

ORGANISM(S): Homo sapiens  

SUBMITTER: Dessen Philippe   Anne Chauchereau  

PROVIDER: E-MTAB-4869 | ArrayExpress | 2018-11-07

REPOSITORIES: ArrayExpress

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Publications

Regulation of eIF4F Translation Initiation Complex by the Peptidyl Prolyl Isomerase FKBP7 in Taxane-resistant Prostate Cancer.

Garrido Marine F MF   Martin Nicolas J-P NJ   Bertrand Matthieu M   Gaudin Catherine C   Commo Frédéric F   El Kalaany Nassif N   Al Nakouzi Nader N   Fazli Ladan L   Del Nery Elaine E   Camonis Jacques J   Perez Franck F   Lerondel Stéphanie S   Le Pape Alain A   Compagno Daniel D   Gleave Martin M   Loriot Yohann Y   Désaubry Laurent L   Vagner Stéphan S   Fizazi Karim K   Chauchereau Anne A  

Clinical cancer research : an official journal of the American Association for Cancer Research 20181015 2


PURPOSE:Targeted therapies that use the signaling pathways involved in prostate cancer are required to overcome chemoresistance and improve treatment outcomes for men. Molecular chaperones play a key role in the regulation of protein homeostasis and are potential targets for overcoming chemoresistance.Experimental Design: We established 4 chemoresistant prostate cancer cell lines and used image-based high-content siRNA functional screening, based on gene-expression signature, to explore mechanis  ...[more]

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