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Oncogene
  • Original Paper
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Regulation of the human poly(ADP-ribose) polymerase promoter by the ETS transcription factor

Oncogenevolume 18, pages3954–3962 (1999)Cite this article

Abstract

Ewing's sarcoma (EWS) cells accumulate elevated steady-state levels of poly (ADP-ribose) polymerase (PARP) mRNA and protein. To understand the molecular mechanisms underlying PARP upregulation, we cloned and analysed the 5′-flanking region of the PARP gene from EWS cells. Nucleotide sequence analysis demonstrated no variations in the PARP promoter region in EWS cells. The PARP promoter encompasses multiple binding motifs for the ETS transcription factor. We have also observed that there is a coordinated up-regulation of the expression of both PARP and ETS1, relative to cells of other human tumor types expressing lower levels of PARP. Transient co-expression of ETS1 in EWS cells resulted in a strong enhancement of PARP-promoter activity. The participation of ETS in the regulation of PARP gene expression was further demonstrated in EWS cells stably transfected withEts1 antisense cDNA constructs. Antisense-mediated down-regulation of endogenous ETS1 resulted in the inhibition of PARP expression in EWS cells, and sensitized these cells to ionizing radiation. These data provide support for ETS regulation of PARP expression levels, and implicate ETS transcription factors in the radiation response of EWS cells.

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Acknowledgements

Authors thank Dr P Ramsamooj for valuable discussions. Drs TS Papas and DK Watson are gratefully acknowledged for providing ETS1-expressing recombinant plasmids and Dr T Ogura for the pBal-CAT construct containing 5′ PARP from human leukocytes. This work was supported by grant PO1-CA74175 from the National Cancer Institute.

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Authors and Affiliations

  1. Department of Radiation Medicine, Lombardi Cancer Center, Georgetown University Medical Center, Research Building, Room E215A, 3970 Reservoir Road, NW, Washington, 20007, DC, USA

    Viatcheslav A Soldatenkov, Amador Albor, Bharvin KR Patel, Roni Dreszer, Anatoly Dritschilo & Vicente Notario

Authors
  1. Viatcheslav A Soldatenkov
  2. Amador Albor
  3. Bharvin KR Patel
  4. Roni Dreszer
  5. Anatoly Dritschilo
  6. Vicente Notario

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Soldatenkov, V., Albor, A., Patel, B.et al. Regulation of the human poly(ADP-ribose) polymerase promoter by the ETS transcription factor.Oncogene18, 3954–3962 (1999). https://doi.org/10.1038/sj.onc.1202778

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