Activation of p65 NF-κB protein by p210BCR – ABL in a myeloid cell line (P210BCR – ABL activates p65 NF-κB) (original) (raw)

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• Published: 06 November 1997

Oncogene volume 15, pages 2267–2275 (1997)Cite this article

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Abstract

The chimeric tyrosine kinase p210BCR – ABL is involved in the pathogenesis of chronic myelogenous leukemia. It transforms immature hematopoietic cells in vitro and abrogates IL-3-dependent growth. The mechanisms by which p210BCR – ABL mediates its oncogenicity are not well elucidated. Identifying transcription factors targeted by the chimeric protein may help to clarify these mechanisms. We have analysed the effect of p210BCR – ABL expression on NF-κB activity in DA1 cells (an IL-3-dependent murine myeloid progenitor cell line). A specific stimulation of NF-κB activity by kinase-active wild-type p210BCR – ABL has been evidenced by transcriptional activation assays. Electrophoretic mobility supershift assays revealed the presence of p65 protein (RelA) DNA binding activity in p210BCR – ABL transformed DA1 cells but not in parental DA1 cells. Activation of RelA in transformed DA1 cells may occur by protein stabilization. Experiments using oligonucleotides antisense to RelA showed that p210BCR – ABL transfected cells failed to survive after IL-3 removal. Moreover, inhibition of cellular growth was shown following treatment of p210BCR – ABL transformed DA1 cells by p65 antisense oligonucleotides. This study suggests that p65 NF-κB may be an effector for p210BCR – ABL and probably contributes to its induced transformation process.

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Authors and Affiliations

1. INSERM U124, Onco-Hématologie Moléculaire, Institut de Recherches sur le Cancer de Lille, place de verdun,
   Malika Hamdane, Marie-Helene David-Cordonnier & Jean Claude D'Halluin
2. 59 045, Lille (cedex), France
   Malika Hamdane, Marie-Helene David-Cordonnier & Jean Claude D'Halluin

Authors

1. Malika Hamdane
2. Marie-Helene David-Cordonnier
3. Jean Claude D'Halluin

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Hamdane, M., David-Cordonnier, MH. & D'Halluin, J. Activation of p65 NF-κB protein by p210BCR – ABL in a myeloid cell line (P210BCR – ABL activates p65 NF-κB).Oncogene 15, 2267–2275 (1997). https://doi.org/10.1038/sj.onc.1201411

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• Received: 31 January 1997
• Revised: 08 July 1997
• Accepted: 07 October 1997
• Issue date: 06 November 1997
• DOI: https://doi.org/10.1038/sj.onc.1201411

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