Ion, Key Laboratory of Carcinogenesis, Department of Health, Changsha, China, 4 Center for Molecular Imaging, Central South University, Changsha, China Background: The latent membrane protein 1 is KRN 633 286370-15-8 encoded by EBV associated, in the majority expressed by EBV- associated tumors in humans and has been suggested that a major mechanism of oncogenic factors EBV-mediated carcinogenesis be. In previous studies we have shown experimentally that the regulation of expression of LMP1 DNAzymes were the radiosensitivity of cells at once and in a xenograft model with M NPC mice to increased hen. Results: In this study we investigated the molecular mechanisms of radiosensitization by downregulation of the LMP1 causes nasopharyngeal cancer. It is best Firmed that LMP1 k Nnte to regulate ATM expression in NPC.
A bioinformatics analysis of the region revealed three attempts ptomoter ATM binding sites for NF-kB. Using a specific inhibitor of NF-kB signaling and dominant negative Limonin inhibitor mutant of IkappaB was shown that the expression in ATM CNE1-LMP1 cells could be efficiently suppressed. The inhibition of expression by LMP1 DNAzyme resulted in a reduction of the activity t of NF-kB DNA binding. We have also shown that the silence of the hen ATM expression by siRNA targeted to ATM cell k Nnte radiosensitivity in LMP1-positive NPC increased to. Conclusions: Together, our results show that ATM expression by LMP1 is NF-kB by directly binding promoter that are regulated by the change in the radiation sensitivity of the NPC in a row. Citation: Ma X, Yang L, Xiao L, Tang M, Liu L, et al.
Down-regulation of EBV-LMP1 radio sensitized nasopharyngeal carcinoma cells via NF-kB regulated ATM expression. PLoS ONE 6: e24647. doi: 10.1371/journal.pone.0024647 Editor: Siyaram Pandey, University of Windsor, Canada is 16th again u February 2011; Accepted Ao t 16, 2011 Ver published 9 November 2011 Copyright: 2011 _ Ma et al. This is an Open Access article distributed under the terms of the Creative Commons Attribution License, which uneingeschr Distribution of spaces permitted use, distribution, and reproduction in any medium, provided the original author and source are credited. Funding: This work was supported by the National Natural Science Foundation of China and National High Technology Research and Development Program of China.
F Sponsors played no R In the study design, data collection and analysis, decision to Ver Publication or preparation of this manuscript. Conflicts of interest: The authors have explained rt that no competing interests exist. * E-mail: LQ Sun hotmail; ycao98 vip.sina ¤ Present address: Cell Transplant and Gene Therapy Institute, Central South University, The 3rd Xiangya H Pital, Changsha, China. The authors contributed equally S to this work. Pr Presentation of the radio-resistance was an obstacle in the clinical facilities for effective therapy against cancer, which will probably be linked to several signaling pathways in different cancers. ATM is a nuclear protein kinase with a 350 kDa kinase-Dom Ne carboxyl-terminal phosphatidylinositol 3-kinase is like. It works as part of a coordinated system that detects DNA breaks will stop temporarily in G1 cells, S, or control points G2 and activates DNA repair.
Cells without functional ATM protein show an increased Hte sensitivity to ionizing radiation and other genotoxic events. Activate NF-kB can k Many genes involved in stress responses, inflammation and programmed cell death. P50 or P50 homodimers / or p65 heterodimers bind to sites p50/c-Rel NF-kB DNA binding in promoter regions of many genes in response to stress, which controls a complex gene network and physiological regulation EEA by NF-kB in response to stress. The high basal activity of NFkB-t in various kinds of cancers to tumor resistance has been associated