作者
Michael C Haffner, Martin J Aryee, Antoun Toubaji, David M Esopi, Roula Albadine, Bora Gurel, William B Isaacs, G Steven Bova, Wennuan Liu, Jianfeng Xu, Alan K Meeker, George Netto, Angelo M De Marzo, William G Nelson, Srinivasan Yegnasubramanian
发表日期
2010/8
期刊
Nature genetics
卷号
42
期号
8
页码范围
668-675
出版商
Nature Publishing Group US
简介
DNA double-strand breaks (DSBs) can lead to the development of genomic rearrangements, which are hallmarks of cancer. Fusions between TMPRSS2, encoding the transmembrane serine protease isoform 2, and ERG, encoding the v-ets erythroblastosis virus E26 oncogene homolog, are among the most common oncogenic rearrangements observed in human cancer. We show that androgen signaling promotes co-recruitment of androgen receptor and topoisomerase II beta (TOP2B) to sites of TMPRSS2-ERG genomic breakpoints, triggering recombinogenic TOP2B-mediated DSBs. Furthermore, androgen stimulation resulted in de novo production of TMPRSS2-ERG fusion transcripts in a process that required TOP2B and components of the DSB repair machinery. Finally, unlike normal prostate epithelium, prostatic intraepithelial neoplasia cells showed strong coexpression of androgen receptor and TOP2B …
引用总数
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