For Publishers
DiscoveryMetadataPeer reviewHostingPublishing
For Researchers
JoinPublishReviewCollect
Register
Blog
About
Search
Advanced search
My ScienceOpen
Search
For Publishers
For Researchers
Blog
About
128
views
37
references
 Top references
cited by
210
    
0 reviews
 Review
0
comments
 Comment
0
recommends
+1 Recommend
0 collections
    0
    shares
      467
      similar
       All similar
      • Record: found
      • Abstract: found
      • Article: not found

      Androgen-induced TOP2B mediated double strand breaks and prostate cancer gene rearrangements

      research-article

      Read this article at

      ScienceOpenPublisherPMC
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          DNA double strand breaks (DSB) can lead to development of genomic rearrangements, which are hallmarks of cancer. TMPRSS2-ERG gene fusions in prostate cancer (PCa) are among the most common genomic rearrangements observed in human cancer. We show that androgen signaling promotes co-recruitment of androgen receptor (AR) and topoisomerase II beta (TOP2B) to sites of TMPRSS2-ERG genomic breakpoints, triggering recombinogenic TOP2B-mediated DSB. Furthermore, androgen stimulation resulted in de novo production of TMPRSS2-ERG fusion transcripts in a process requiring TOP2B and components of DSB repair machinery. Finally, unlike normal prostate epithelium, prostatic intraepithelial neoplasia (PIN) cells showed strong co-expression of AR and TOP2B. These findings implicate androgen-induced TOP2B-mediated DSB in generating TMPRSS2-ERG rearrangements.

          Related collections

          Most cited references37

          • Record: found
          • Abstract: found
          • Article: not found

          Inflammation in prostate carcinogenesis.

          Angelo M. De Marzo, Elizabeth A. Platz, Siobhan Sutcliffe … (2007)
          About 20% of all human cancers are caused by chronic infection or chronic inflammatory states. Recently, a new hypothesis has been proposed for prostate carcinogenesis. It proposes that exposure to environmental factors such as infectious agents and dietary carcinogens, and hormonal imbalances lead to injury of the prostate and to the development of chronic inflammation and regenerative 'risk factor' lesions, referred to as proliferative inflammatory atrophy (PIA). By developing new experimental animal models coupled with classical epidemiological studies, genetic epidemiological studies and molecular pathological approaches, we should be able to determine whether prostate cancer is driven by inflammation, and if so, to develop new strategies to prevent the disease.
          Article 0 comments Cited 405 times – based on 0 reviews     Review now
            Bookmark
            • Record: found
            • Abstract: found
            • Article: found
            Is Open Access

            γ-H2AX in recognition and signaling of DNA double-strand breaks in the context of chromatin

            Andrea Kinner, Wenqi Wu, Christian Staudt … (2008)
            DNA double-strand breaks (DSBs) are extremely dangerous lesions with severe consequences for cell survival and the maintenance of genomic stability. In higher eukaryotic cells, DSBs in chromatin promptly initiate the phosphorylation of the histone H2A variant, H2AX, at Serine 139 to generate γ-H2AX. This phosphorylation event requires the activation of the phosphatidylinositol-3-OH-kinase-like family of protein kinases, DNA-PKcs, ATM, and ATR, and serves as a landing pad for the accumulation and retention of the central components of the signaling cascade initiated by DNA damage. Regions in chromatin with γ-H2AX are conveniently detected by immunofluorescence microscopy and serve as beacons of DSBs. This has allowed the development of an assay that has proved particularly useful in the molecular analysis of the processing of DSBs. Here, we first review the role of γ-H2AX in DNA damage response in the context of chromatin and discuss subsequently the use of this modification as a surrogate marker for mechanistic studies of DSB induction and processing. We conclude with a critical analysis of the strengths and weaknesses of the approach and present some interesting applications of the resulting methodology.
            Article 0 comments Cited 365 times – based on 0 reviews     Review now
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Ataxia-telangiectasia: from a rare disorder to a paradigm for cell signalling and cancer.

              Martin F. Lavin (2008)
              First described over 80 years ago, ataxia-telangiectasia (A-T) was defined as a clinical entity 50 years ago. Although not encountered by most clinicians, it is a paradigm for cancer predisposition and neurodegenerative disorders and has a central role in our understanding of the DNA-damage response, signal transduction and cell-cycle control. The discovery of the protein A-T mutated (ATM) that is deficient in A-T paved the way for rapid progress on understanding how ATM functions with a host of other proteins to protect against genome instability and reduce the risk of cancer and other pathologies.
              Article 0 comments Cited 229 times – based on 0 reviews     Review now
                Bookmark
                All references

                Author and article information

                Journal
                Journal ID (nlm-journal-id): 9216904
                Journal ID (pubmed-jr-id): 2419
                Journal ID (nlm-ta): Nat Genet
                Journal ID (iso-abbrev): Nat. Genet.
                Title: Nature genetics
                ISSN (Print): 1061-4036
                ISSN (Electronic): 1546-1718
                Publication date Nihms-submitted: 4 August 2011
                Publication date (Electronic): 04 July 2010
                Publication date (Print): August 2010
                Publication date PMC-release: 17 August 2011
                Volume: 42
                Issue: 8
                Pages: 668-675
                Affiliations
                [1 ]Sidney Kimmel Comprehensive Cancer Center, School of Medicine, Johns Hopkins University, 1650 Orleans Street, Baltimore, Maryland, 21231 USA
                [2 ]Department of Biostatistics, Bloomberg School of Public Health, School of Medicine, Johns Hopkins University, 1650 Orleans Street, Baltimore, Maryland, 21231 USA
                [3 ]Department of Pathology, School of Medicine, Johns Hopkins University, 1650 Orleans Street, Baltimore, Maryland, 21231 USA
                [4 ]Brady Urological Institute, School of Medicine, Johns Hopkins University, 1650 Orleans Street, Baltimore, Maryland, 21231 USA
                [5 ]Center for Cancer Genomics, Wake Forrest University Health Sciences, Medical Center Boulevard, Wake Forrest, North Carolina, 27157 USA
                Author notes
                Correspondence and requests for materials should be addressed to S.Y. ( syegnasu@ 123456jhmi.edu ) or W.G.N. ( bnelson@ 123456jhmi.edu )
                [*]

                These authors contributed equally to this work.

                Article
                Manuscript ID: nihpa210961
                DOI: 10.1038/ng.613
                PMC ID: 3157086
                PubMed ID: 20601956
                SO-VID: 26d6eb7e-2b26-4d65-a559-b2b5b8363c2a
                License:

                Users may view, print, copy, download and text and data- mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#terms

                History
                Funding
                Funded by: National Cancer Institute : NCI
                Award ID: R01 CA070196-13 || CA
                Funded by: National Cancer Institute : NCI
                Award ID: P50 CA058236-16 || CA
                Categories
                Subject: Article

                ScienceOpen disciplines: Genetics
                Data availability:
                ScienceOpen disciplines: Genetics

                Comments

                Comment on this article

                scite_

                Similar content467

                See all similar

                Cited by205

                See all cited by

                Most referenced authors1,035

                See all reference authors