We have an ongoing interest in the role of methylation changes in cancer as well as the roles of androgen and estrogen receptor signaling in prostate and breast cancer. We demonstrated that in castration-resistant prostate cancer, androgen receptor signaling still plays a major role, but that the binding sites are substantially remodeled (Decker et al, 2012). Further we have shown that amplification of the estrogen-receptor is one potential mechanism amongst various mutations and fusions by which estrogen receptor is over-expressed in endocrine therapy resistant breast cancer (Li et al. 2013). Lastly, we mapped DNA methylation genome-wide in endocrine therapy resistant breast cancer and demonstrated that epigenetic activation of the EP4 receptor was required for estrogen-independent cell proliferation (Hiken et al. 2017).
Recent Relevant Publications
Hiken JF, McDonald JI, Decker KF, Sanchez C, Hoog J, VanderKraats ND, Jung KL, Akinhanmi M, Rois LE, Ellis MJ, Edwards JR. Epigenetic activation of the prostaglandin receptor EP4 promotes resistance to endocrine therapy for breast cancer. Oncogene. 2017 Apr 20;36(16):2319-2327. doi: 10.1038/onc.2016.397. Epub 2016 Nov 21. PubMed PMID: 27869171; PubMed Central PMCID: PMC5398938.
Cruickshanks HA, McBryan T, Nelson DM, Vanderkraats ND, Shah PP, van Tuyn J, Singh Rai T, Brock C, Donahue G, Dunican DS, Drotar ME, Meehan RR, Edwards JR, Berger SL, Adams PD. Senescent cells harbour features of the cancer epigenome. Nat Cell Biol. 2013 Dec;15(12):1495-506. doi: 10.1038/ncb2879. Epub 2013 Nov 24. PubMed PMID: 24270890; PubMed Central PMCID: PMC4106249.
Lund K, Cole JJ, VanderKraats ND, McBryan T, Pchelintsev NA, Clark W, Copland M, Edwards JR, Adams PD. DNMT inhibitors reverse a specific signature of aberrant promoter DNA methylation and associated gene silencing in AML. Genome Biol. 2014 Aug 30;15(8):406. doi: 10.1186/s13059-014-0406-2. PubMed PMID: 25315154; PubMed Central PMCID: PMC4165364.
Decker KF, Zheng D, He Y, Bowman T, Edwards JR, Jia L. Persistent androgen receptor-mediated transcription in castration-resistant prostate cancer under androgen-deprived conditions. Nucleic Acids Res. 2012 Nov;40(21):10765-79. doi: 10.1093/nar/gks888. Epub 2012 Sep 27. PubMed PMID: 23019221; PubMed Central PMCID: PMC3510497.