Nrf2 Expression Is Regulated by Epigenetic Mechanisms in Prostate Cancer of TRAMP Mice

Nuclear factor-erythroid 2 p45-related factor 2 (Nrf2) is a transcription factor which regulates the expression of many cytoprotective genes. In the present study, we found that the expression of Nrf2 was suppressed in prostate tumor of the Transgenic Adenocarcinoma of Mouse Prostate (TRAMP) mice. Similarly, the expression of Nrf2 and the induction of NQO1 were also substantially suppressed in tumorigenic TRAMP C1 cells but not in non-tumorigenic TRAMP C3 cells. Examination of the promoter region of the mouse Nrf2 gene identified a CpG island, which was methylated at specific CpG sites in prostate TRAMP tumor and in TRAMP C1 cells but not in normal prostate or TRAMP C3 cells, as shown by bisulfite genomic sequencing. Reporter assays indicated that methylation of these CpG sites dramatically inhibited the transcriptional activity of the Nrf2 promoter. Chromatin immunopreceipitation (ChIP) assays revealed increased binding of the methyl-CpG-binding protein 2 (MBD2) and trimethyl-histone H3 (Lys9) proteins to these CpG sites in the TRAMP C1 cells as compared to TRAMP C3 cells. In contrast, the binding of RNA Pol II and acetylated histone H3 to the Nrf2 promoter was decreased. Furthermore, treatment of TRAMP C1 cells with DNA methyltransferase (DNMT) inhibitor 5-aza-2′-deoxycytidine (5-aza) and histone deacetylase (HDAC) inhibitor trichostatin A (TSA) restored the expression of Nrf2 as well as the induction of NQO1 in TRAMP C1 cells. Taken together, these results indicate that the expression of Nrf2 is suppressed epigenetically by promoter methylation associated with MBD2 and histone modifications in the prostate tumor of TRAMP mice. Our present findings reveal a novel mechanism by which Nrf2 expression is suppressed in TRAMP prostate tumor, shed new light on the role of Nrf2 in carcinogenesis and provide potential new directions for the detection and prevention of prostate cancer

Observation of the diphoton decay of the Higgs boson and measurement of its properties

Peer reviewe

Precise determination of the mass of the Higgs boson and tests of compatibility of its couplings with the standard model predictions using proton collisions at 7 and 8 TeV

Peer reviewe

Search for Dark Matter and Supersymmetry with a Compressed Mass Spectrum in the Vector Boson Fusion Topology in Proton-Proton Collisions at root s=8 TeV

Peer reviewe

Search for new physics in the multijet and missing transverse momentum final state in proton-proton collisions at √s=8 Tev

Peer reviewe

Measurements of the tt¯ charge asymmetry using the dilepton decay channel in pp collisions at √s=7 TeV

Peer reviewe

Measurement of the production cross section ratio σ(χb2(1P))/σ(χb1(1P))in pp collisions at √s=8TeV

A measurement of the production cross section ratio σ(χb2(1P))/σ(χb1(1P))σ(χb2(1P))/σ(χb1(1P)) is presented. The χb1(1P)χb1(1P) and χb2(1P)χb2(1P) bottomonium states, promptly produced in pp collisions at View the MathML sources=8 TeV, are detected by the CMS experiment at the CERN LHC through their radiative decays χb1,2(1P)→ϒ(1S)+γχb1,2(1P)→ϒ(1S)+γ. The emitted photons are measured through their conversion to e+e−e+e− pairs, whose reconstruction allows the two states to be resolved. The ϒ(1S)ϒ(1S) is measured through its decay to two muons. An event sample corresponding to an integrated luminosity of 20.7 fb−120.7 fb−1 is used to measure the cross section ratio in a phase-space region defined by the photon pseudorapidity, |ηγ|<1.0|ηγ|<1.0; the ϒ(1S)ϒ(1S) rapidity, |yϒ|<1.5|yϒ|<1.5; and the ϒ(1S)ϒ(1S) transverse momentum, View the MathML source7<pTϒ<40 GeV. The cross section ratio shows no significant dependence on the ϒ(1S)ϒ(1S) transverse momentum, with a measured average value of View the MathML source0.85±0.07(stat+syst)±0.08(BF), where the first uncertainty is the combination of the experimental statistical and systematic uncertainties and the second is from the uncertainty in the ratio of the χbχb branching fractions

Measurement of the Zγ production cross section in pp collisions at 8 TeV and search for anomalous triple gauge boson couplings

Open Access, Copyright CERN, for the benefit of the CMS Collaboration. Article funded by SCOAP3.Abstract: The cross section for the production of Zγ in proton-proton collisions at 8 TeV is measured based on data collected by the CMS experiment at the LHC corresponding to an integrated luminosity of 19.5 fb−1. Events with an oppositely-charged pair of muons or electrons together with an isolated photon are selected. The differential cross section as a function of the photon transverse momentum is measured inclusively and exclusively, where the exclusive selection applies a veto on central jets. The observed cross sections are compatible with the expectations of next-to-next-to-leading-order quantum chromodynamics. Limits on anomalous triple gauge couplings of ZZγ and Zγγ are set that improve on previous experimental results obtained with the charged lepton decay modes of the Z boson

Indications of suppression of excited Υ states in Pb-Pb collisions at √sNN = 2.76TeV

This is the pre-print version of the Published Article which can be accessed from the link below.A comparison of the relative yields of Υ resonances in the μ+μ- decay channel in Pb-Pb and pp collisions at a center-of-mass energy per nucleon pair of 2.76 TeV is performed with data collected with the CMS detector at the LHC. Using muons of transverse momentum above 4  GeV/c and pseudorapidity below 2.4, the double ratio of the Υ(2S) and Υ(3S) excited states to the Υ(1S) ground state in Pb-Pb and pp collisions, [Υ(2S+3S)/Υ(1S)]Pb-Pb/[Υ(2S+3S)/Υ(1S)]pp, is found to be 0.31-0.15+0.19(stat)±0.03(syst). The probability to obtain the measured value, or lower, if the true double ratio is unity, is calculated to be less than 1%