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Urology news 17 Feb.2014
David P. Labbé1,2, Dawid G. Nowak4, Geneviève Deblois1,3, Laurent Lessard5, Vincent Giguère1,2,3, Lloyd C. Trotman4, and Michel L. Tremblay1,2,31Goodman Cancer Research Centre; 2Department of Medicine, Division of Experimental Medicine; 3Department of Biochemistry and Oncology, McGill University, Montréal, Québec, Canada; 4Cold Spring Harbor Laboratory, NY; and 5Department of Molecular Oncology, John Wayne Cancer Institute at St. John's Health Center, Santa Monica, California
The 20q13 chromosomal region has been previously identified as the hereditary prostate cancer genetic-susceptibility locus on chromosome 20 (HPC20).
In this study, the 20q13 region was shown to be frequently co-amplified with the androgen receptor (AR) in metastatic prostate cancer. Furthermore, the AR signaling 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 of most genes located on the 20q13 CAR. Moreover, amplification of AR 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-resistant metastatic 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.
Mol Cancer Res; 12(2); 1–6. ©2013 AACR. December 3, 2013.
©2013 American Association for Cancer Research.