Labbé, D. P., Nowak, D. G., Deblois, G., Lessard, L., Giguère, V., Trotman, L. C., Tremblay, M. L. (2014) Prostate cancer genetic-susceptibility locus on chromosome 20q13 is amplified and coupled to androgen receptor-regulation in metastatic tumors. Molecular Cancer Research, 12 (2). pp. 184-189. ISSN 15417786 (ISSN)
Abstract
The 20q13 chromosomal region has been previously identified as the hereditary prostate cancer geneticsusceptibility locus on chromosome 20 (HPC20). In this study, the 20q13 region was shown to be frequently co-amplified with the androgen receptor (AR) inmetastatic prostate cancer. Furthermore, the ARsignaling axis,which plays an essential role in the pathogenesis of prostate cancer, was demonstrated to be central to the regulation of the 20q13 common amplified region (CAR). High-resolution mapping analyses revealed hot spots of AR recruitment to response elements in the vicinity ofmost genes located on the 20q13CAR.Moreover, amplification ofAR significantly co-occurred with CAR amplification on 20q13 and it was confirmed that the majority of AR-bound genes on the 20q13 CAR were indeed regulated by androgens. These data reveal that amplification of the AR is tightly linked to amplification of the AR-regulated CAR region on 20q13. These results suggest that the cross-talk between gene amplification and gene transcription is an important step in the development of castration-resistantmetastatic disease. Implications: These novel results are a noteworthy example of the cross-talk between gene amplification and gene transcription in the development of advanced prostate cancer. Visual Overview: http://mcr.aacrjournals.org/content/early/2014/02/07/1541-7786.MCR-13-0477/F1.large.jpg.
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