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      Expression and anti-apoptotic function of TRAF4 in human breast cancer MCF-7 cells

      research-article
      1 , 2 , 3 , 1
      Oncology Letters
      D.A. Spandidos
      TRAF4, apoptosis, breast cancer, siRNA

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          Abstract

          Tumor necrosis factor (TNF) receptor-associated factor 4 (TRAF4) was initially identified as a gene amplified and overexpressed in breast carcinoma. The present study investigated the expression and anti-apoptotic function of TRAF4 in human breast cancer MCF-7 cells. TRAF4 was found to be localized in the cytoplasm and nuclei of MCF-7 cells by immunofluorescence staining and western blotting. The expression of TRAF4 in normal MCF-10A breast cells was found to be lower than in MCF-7 and MDA-MB-231 breast cancer cells. Following TNF-α treatment, TRAF4 depletion by siRNA in the MCF-7 cells was observed to suppress cell proliferation and the nuclear expression of nuclear factor κB was significantly reduced. The percentage of early apoptotic cells in the MCF-7 cells was augmented upon TRAF4-knockdown, and an increase in G 1 phase cells and a decrease in S phase cells was detected. These results indicate that TRAF4 has anti-apoptotic effects on apoptosis induced by TNF-α in MCF-7 cells.

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          Most cited references20

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          TRAF2-mediated activation of NF-kappa B by TNF receptor 2 and CD40.

          TNF receptor-associated factor (TRAF) proteins are candidate signal transducers that associate with the cytoplasmic domains of members of the tumor necrosis factor (TNF) receptor superfamily. The role of TRAFs in the TNF-R2 and CD40 signal transduction pathways, which result in the activation of transcription factor NF-kappa B, was investigated. Overexpression of TRAF2, but not TRAF1 or TRAF3, was sufficient to induce NF-kappa B activation. A truncated derivative of TRAF2 lacking an amino-terminal RING finger domain was a dominant-negative inhibitor of NF-kappa B activation mediated by TNF-R2 and CD40. Thus, TRAF2 is a common mediator of TNF-R2 and CD40 signaling.
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            All TRAFs are not created equal: common and distinct molecular mechanisms of TRAF-mediated signal transduction.

            The tumor necrosis factor (TNF) receptor associated factors (TRAFs) have emerged as the major signal transducers for the TNF receptor superfamily and the interleukin-1 receptor/Toll-like receptor (IL-1R/TLR) superfamily. TRAFs collectively play important functions in both adaptive and innate immunity. Recent functional and structural studies have revealed the individuality of each of the mammalian TRAFs and advanced our understanding of the underlying molecular mechanisms. Here, we examine this functional divergence among TRAFs from a perspective of both upstream and downstream TRAF signal transduction pathways and of signaling-dependent regulation of TRAF trafficking. We raise additional questions and propose hypotheses regarding the molecular basis of TRAF signaling specificity.
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              Tumor necrosis factor receptor-associated factors (TRAFs)--a family of adapter proteins that regulates life and death.

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                Author and article information

                Journal
                Oncol Lett
                Oncol Lett
                OL
                Oncology Letters
                D.A. Spandidos
                1792-1074
                1792-1082
                February 2014
                25 November 2013
                25 November 2013
                : 7
                : 2
                : 411-414
                Affiliations
                [1 ]Department of Pathology, The First Affiliated Hospital and College of Basic Medical Sciences of China Medical University, Shenyang, Liaoning 110001, P.R. China
                [2 ]Department of Assisted Reproduction, Shenyang Women’s and Children’s Hospital, Shenyang, Liaoning 110001, P.R. China
                [3 ]Department of Neurosurgery, The First Affiliated Hospital, China Medical University, Shenyang, Liaoning 110001, P.R. China
                Author notes
                Correspondence to: Professor Xiaoyi Mi, Department of Pathology, The First Affiliated Hospital and College of Basic Medical Sciences of China Medical University, 92 Beima Road, Shenyang, Liaoning 110001, P.R. China, E-mail: xiaoyi_mi@ 123456163.com
                Article
                ol-07-02-0411
                10.3892/ol.2013.1703
                3881200
                24396457
                b361f26d-6ebd-40cb-bb1b-9cefa5d5b068
                Copyright © 2014, Spandidos Publications

                This is an open-access article licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported License. The article may be redistributed, reproduced, and reused for non-commercial purposes, provided the original source is properly cited.

                History
                : 05 May 2013
                : 12 November 2013
                Categories
                Articles

                Oncology & Radiotherapy
                sirna,traf4,apoptosis,breast cancer
                Oncology & Radiotherapy
                sirna, traf4, apoptosis, breast cancer

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