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

• Published in: Leukemia Vol. 16; no. 5; pp. 940 - 948
• Main Authors: RYBNER, C, HILLION, J, SABRAOUI, T, LANOTTE, M, BOTTI, J
• Format: Journal Article
• Language: English
• Published: London Nature Publishing 01.05.2002; Nature Publishing Group
• Subjects: Antineoplastic agents; Biological and medical sciences; Blood; Blood platelets; Cell Differentiation; Cells; Chemotherapy; Creutzfeldt-Jakob disease; Differentiation; Dose-Response Relationship, Drug; Down-Regulation - drug effects; Down-Regulation - genetics; Gene expression; Genetic aspects; Granulocytes; Granulocytes - cytology; Humans; Kinetics; Leukemia; Leukemia - pathology; Leukocytes (granulocytic); Maturation; Medical sciences; Membrane proteins; Membrane Proteins - drug effects; Membrane Proteins - metabolism; Membranes; mRNA; Pathogenesis; Pharmacology. Drug treatments; Physiological aspects; Prion diseases; Prion protein; Prions; Protein biosynthesis; Protein expression; Protein synthesis; Proteins; PrPC Proteins - drug effects; PrPC Proteins - genetics; PrPC Proteins - metabolism; Retinoic acid; Retinoids; Ribonucleic acid; Risk factors; RNA; RNA, Messenger - drug effects; RNA, Messenger - metabolism; Tretinoin; Tretinoin - pharmacology; Tumor cell lines; Tumor Cells, Cultured; France; Human; Membrane protein; Leukemia; Retinoid; Malignant hemopathy; Cell differentiation; Biological activity; Sialoglycoproteins; Regulation(control); Established cell line; Prion; Prion protein; Tumor cell; Tretinoin
• ISSN: 0887-6924; 1476-5551
• DOI: 10.1038/sj.leu.2402443

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.