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• W1889643605 abstract "// Caterina Mancarella 1 , Irene Casanova-Salas 2 , Ana Calatrava 3 , Selena Ventura 1 , Cecilia Garofalo 1 , José Rubio-Briones 4 , Vera Magistroni 5 , Maria Cristina Manara 1 , José Antonio López-Guerrero 2, * , Katia Scotlandi 1, * 1 CRS Development of Biomolecular Therapies, Experimental Oncology Lab, Rizzoli Orthopaedic Institute, Bologna, Italy 2 Laboratory of Molecular Biology, Fundación Instituto Valenciano de Oncología, Valencia, Spain 3 Department of Pathology, Fundación Instituto Valenciano de Oncología, Valencia, Spain 4 Department of Urology, Fundación Instituto Valenciano de Oncología, Valencia, Spain 5 Department of Health Sciences, University of Milano-Bicocca, Monza, Italy * These authors have shared senior authorship Correspondence to: Katia Scotlandi, e-mail: katia.scotlandi@ior.it Keywords: insulin-like growth factor receptor 1, prostate cancer, ETS fusion genes, anti-IGF-1R agents Received: November 04, 2014      Accepted: February 23, 2015      Published: March 27, 2015 ABSTRACT Identifying patients who may benefit from targeted therapy is an urgent clinical issue in prostate cancer (PCa). We investigated the molecular relationship between TMPRSS2-ERG (T2E) fusion gene and insulin-like growth factor receptor (IGF-1R) to optimize the use of IGF-1R inhibitors. IGF-1R was analyzed in cell lines and in radical prostatectomy specimens in relation to T2E status. ERG binding to IGF-1R promoter was evaluated by chromatin immunoprecipitation (ChIP). Sensitivity to anti-IGF-1R agents was evaluated alone or in combination with anti-androgen abiraterone acetate in vitro at basal levels or upon ERG modulation. IGF-1R analysis performed in PCa cells or clinical samples showed that T2E expression correlated with higher IGF-1R expression at mRNA and protein levels. Genetic modulation of ERG directly affected IGF-1R protein levels in vitro . ChIP analysis showed that ERG binds IGF-1R promoter and that promoter occupancy is higher in T2E-positive cells. IGF-1R inhibition was more effective in cell lines expressing the fusion gene and combination of IGF-1R inhibitors with abiraterone acetate produced synergistic effects in T2E-expressing cells. Here, we provide the rationale for use of T2E fusion gene to select PCa patients for anti-IGF-1R treatments. The combination of anti-IGF-1R-HAbs with an anti-androgen therapy is strongly advocated for patients expressing T2E." @default.
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• W1889643605 date "2015-03-27" @default.
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• W1889643605 title "ERG deregulation induces IGF-1R expression in prostate cancer cells and affects sensitivity to anti-IGF-1R agents" @default.
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• W1889643605 doi "https://doi.org/10.18632/oncotarget.3425" @default.
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