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@INPROCEEDINGS{Dahmen:255692,
      author       = {Dahmen, Volker and Kriehuber, Ralf},
      title        = {{I}nduction of the chromosomal translocation t(14;18) by
                      targeting the{BCL}-2 locus with specific binding
                      {I}-125-labeled {T}riplex-{F}orming oligonucleotides},
      reportid     = {FZJ-2015-05824},
      year         = {2015},
      abstract     = {Triplex-Forming oligonucleotides (TFO) are able to bind DNA
                      in a sequence specific manner and are a promising tool to
                      manipulate genes or gene regulatory units in a cellular
                      environment. TFO possess a therapeutic potential e.g. as a
                      carrier molecule for Alpha- or Auger-Electron-Emitter (AEE)
                      to target specific DNA sequences in tumor cells. We
                      established a method for the effective labeling of TFO with
                      the AEE Iodine-125 (I-125) and analyzed the influence of
                      I-125-labeled TFO in SCL-II cells on gene expression and
                      translocation frequency of the human BCL2 gene. The TFO-BCL2
                      employed in the present study binds to the BCL2 gene at
                      approximately 5400 bp upstream of the 3´-end. TFO labeling
                      with I-125 was performed using the primer extension method.
                      SCL-II cells were transfected with TFO via electroporation
                      and subsequently stored at -150°C for decay accumulation up
                      to a range from 100 to 330 decays/cell. SCL-II cells either
                      transfected with I-125-labeled multi-binding TFO (>300,000
                      targets per genome) or transfected with non-labeled TFO-BCL2
                      served as controls. Monitoring of BCL2 translocations was
                      done with the Fluorescence-In-Situ-Hybridization (FISH)
                      method. The utilized FISH probes were designed to detect a
                      translocation of the BCL2 gene from chromosome 18 to
                      chromosome 14, a common translocation found in follicular
                      lymphomas leading to an overexpression of BCL-2 protein.
                      Analysis of BCL2 gene expression levels was done via
                      quantitative Real-Time PCR on the Real Time PCR System 7500
                      (Applied Biosystems).The relative gene expression of BCl-2
                      in I-125-TFO-BCL2 transfected cells showed a significant
                      up-regulation when compared to the controls. Control SCL-II
                      cells were either transfected with I-125-labeled
                      multi-binding TFO (>300,000 targets per genome) or
                      non-labeled TFO-BCL2. Analysis of the BCL2 t(14;18)
                      translocation frequency revealed a significant 1.8- to
                      2-fold increase when compared to the control cells.We
                      conclude that I-125 decays within the BCL2 gene facilitates
                      the occurrence of the t(14;18) chromosomal translocation in
                      SCL-II cells and that the increased translocation frequency
                      of t(14;18) contributes to the observed overall enhanced
                      BCL-2 expression. However, it seems unlikely that these rare
                      translocation events fully explain the observed enhanced
                      gene expression of BCL-2.Funded by Bundesministerium für
                      Bildung und Forschung (BMBF), Grant 02NUK005A},
      month         = {May},
      date          = {2015-05-25},
      organization  = {15th International Congress of
                       Radiation Reasearch, Kyoto (Japan), 25
                       May 2015 - 29 May 2015},
      subtyp        = {After Call},
      cin          = {S-US},
      cid          = {I:(DE-Juel1)S-US-20090406},
      pnm          = {899 - ohne Topic (POF3-899)},
      pid          = {G:(DE-HGF)POF3-899},
      typ          = {PUB:(DE-HGF)24},
      url          = {https://juser.fz-juelich.de/record/255692},
}