NR AKGT
AU Rybner,C.; Hillion,J.; Sahraoui,T.; Lanotte,M.; Botti,J.
TI All-trans retinoic acid down-regulates prion protein expression independently of granulocyte maturation
QU Leukemia 2002 May; 16(5): 940-8
PT journal article
AB 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.
MH Cell Differentiation; Dose-Response Relationship, Drug; Down-Regulation/drug effects/genetics; Granulocytes/*cytology; Human; Kinetics; Leukemia/pathology; Membrane Proteins/drug effects/metabolism; PrPc Proteins/drug effects/genetics/*metabolism; RNA, Messenger/drug effects/metabolism; Support, Non-U.S. Gov't; Tretinoin/*pharmacology; Tumor Cells, Cultured
AD INSERM U-496, Institut Universitaire d'Hematologie (IUH), Hopital Saint-Louis, Paris, France.
SP englisch
PO England