dc.date.accessioned | 2018-01-23T14:01:40Z | |
dc.date.available | 2018-01-23T14:01:40Z | |
dc.date.created | 2017-08-30T16:14:30Z | |
dc.date.issued | 2017 | |
dc.identifier.citation | Barfeld, Stefan Jörg Urbanucci, Alfonso Itkonen, Harri Fazli, Ladan Hicks, Jessica L. Thiede, Bernd Rennie, Paul S. Yegnasubramanian, Srinivasan DeMarzo, Angelo M. Mills, Ian Geoffrey . c-Myc antagonises the transcriptional activity of the androgen receptor in prostate cancer affecting key gene networks. EBioMedicine. 2017, 18, 83-93 | |
dc.identifier.uri | http://hdl.handle.net/10852/59676 | |
dc.description.abstract | Prostate cancer (PCa) is the most common non-cutaneous cancer in men. The androgen receptor (AR), a ligand-activated transcription factor, constitutes the main drug target for advanced cases of the disease. However, a variety of other transcription factors and signaling networks have been shown to be altered in patients and to influence AR activity. Amongst these, the oncogenic transcription factor c-Myc has been studied extensively in multiple malignancies and elevated protein levels of c-Myc are commonly observed in PCa. Its impact on AR activity, however, remains elusive. In this study, we assessed the impact of c-Myc overexpression on AR activity and transcriptional output in a PCa cell line model and validated the antagonistic effect of c-MYC on AR-targets in patient samples. We found that c-Myc overexpression partially reprogrammed AR chromatin occupancy and was associated with altered histone marks distribution, most notably H3K4me1 and H3K27me3. We found c-Myc and the AR co-occupy a substantial number of binding sites and these exhibited enhancer-like characteristics. Interestingly, c-Myc overexpression antagonised clinically relevant AR target genes. Therefore, as an example, we validated the antagonistic relationship between c-Myc and two AR target genes, KLK3 (alias PSA, prostate specific antigen), and Glycine N-Methyltransferase (GNMT), in patient samples. Our findings provide unbiased evidence that MYC overexpression deregulates the AR transcriptional program, which is thought to be a driving force in PCa. | en_US |
dc.language | EN | |
dc.rights | Attribution-NonCommercial-NoDerivatives 4.0 International | |
dc.rights.uri | https://creativecommons.org/licenses/by-nc-nd/4.0/ | |
dc.title | c-Myc antagonises the transcriptional activity of the androgen receptor in prostate cancer affecting key gene networks | en_US |
dc.type | Journal article | en_US |
dc.creator.author | Barfeld, Stefan Jörg | |
dc.creator.author | Urbanucci, Alfonso | |
dc.creator.author | Itkonen, Harri | |
dc.creator.author | Fazli, Ladan | |
dc.creator.author | Hicks, Jessica L. | |
dc.creator.author | Thiede, Bernd | |
dc.creator.author | Rennie, Paul S. | |
dc.creator.author | Yegnasubramanian, Srinivasan | |
dc.creator.author | DeMarzo, Angelo M. | |
dc.creator.author | Mills, Ian Geoffrey | |
cristin.unitcode | 185,57,0,0 | |
cristin.unitname | Norsk Senter for Molekylærmedisin | |
cristin.ispublished | true | |
cristin.fulltext | original | |
cristin.qualitycode | 1 | |
dc.identifier.cristin | 1490017 | |
dc.identifier.bibliographiccitation | info:ofi/fmt:kev:mtx:ctx&ctx_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.jtitle=EBioMedicine&rft.volume=18&rft.spage=83&rft.date=2017 | |
dc.identifier.jtitle | EBioMedicine | |
dc.identifier.volume | 18 | |
dc.identifier.startpage | 83 | |
dc.identifier.endpage | 93 | |
dc.identifier.doi | http://dx.doi.org/10.1016/j.ebiom.2017.04.006 | |
dc.identifier.urn | URN:NBN:no-62353 | |
dc.type.document | Tidsskriftartikkel | en_US |
dc.type.peerreviewed | Peer reviewed | |
dc.source.issn | 2352-3964 | |
dc.identifier.fulltext | Fulltext https://www.duo.uio.no/bitstream/handle/10852/59676/1/2017%2BBarfeld_Mills_EBioMed_c-MycPCa.pdf | |
dc.type.version | PublishedVersion | |