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All-trans retinoic acid down-regulates prion protein expression independently of granulocyte maturation

Leukemia volume 16, pages 940–948 (2002)Cite this article

Abstract

The cellular prion protein (PrPc) is a sialoglycoprotein involved in the pathogenesis of prion diseases. It has been identified at the plasma membrane of several cell types. All-trans retinoic acid (ATRA) is known to induce differentiation of human leukemia cell lines in vitro. PrPc messenger ribonucleic acid (mRNA) and protein are down-regulated upon ATRA-induced differentiation of HL60 cells. In this report, we have investigated the regulation of PrPc mRNA and protein expression during ATRA-treatment of maturation-sensitive (NB4) and -resistant (NB4-R1 and NB4-R2) cell lines. In ATRA-induced maturation of NB4 cells, down-regulation of PrPc mRNA and protein were observed. We also show that down-regulation of PrPc mRNA is dependent on protein synthesis. Moreover, the same down-regulation of prion protein by ATRA was observed at the surface of maturation-resistant, ATRA-responsive NB4-R1 cells. In contrast, the maturation-resistant and ATRA-unresponsive NB4-R2 subline showed no variation in membrane prion protein expression. These results demonstrate a dissociation between the regulation of prion protein expression by ATRA and the process of granulocyte maturation. We propose that retinoids should be investigated further as a preventive strategy to slow down prion disease progression.

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Acknowledgements

The authors are indebted to Mrs C Doliger and Mr M Schmid from the Service Commun d'Imageries Cellulaires et Moléculaires of the Institut Universitaire d'Hématologie (Hôpital Saint-Louis) for confocal microscopy. This work was supported by grants from INSERM, the Association pour la Recherche contre le Cancer (ARC No. 9884, No. 5707), the Ministère de l'Enseignement Supérieur, de la Recherche Scientifique et Technique (MESRST No. 98C0275), the INTAS, the Coopération Franco-Algérienne (ALG4B207B). C Rybner is a recipient of a fellowship from the Ligue Nationale contre le Cancer.

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  1. INSERM U-496, Institut Universitaire d'Hématologie (IUH), Hôpital Saint-Louis, Paris, France

    C Rybner, J Hillion, T Sahraoui, M Lanotte & J Botti

  2. Département de Biologie, Université Es-Sénia, Faculté des Sciences, Oran, Algeria

    T Sahraoui

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Rybner, C., Hillion, J., Sahraoui, T. et al. All-trans retinoic acid down-regulates prion protein expression independently of granulocyte maturation. Leukemia 16, 940–948 (2002). https://doi.org/10.1038/sj.leu.2402443

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