@article{31b5babe212e40508eb41cc4d4910641,
title = "ATRA-induced upregulation of Beclin 1 prolongs the life span of differentiated acute promyelocytic leukemia cells",
abstract = "Acute promyelocytic leukemia (APL) results from a blockade of granulocyte differentiation at the promyelocytic stage. All-trans retinoic acid (ATRA) induces clinical remission in APL patients by enhancing the rapid differentiation of APL cells and the clearance of PML-RAR?, APL's hallmark oncoprotein. In the present study, we demonstrated that both autophagy and Beclin 1, an autophagic protein, are upregulated during the course of ATRA-induced neutrophil/granulocyte differentiation of an APL-derived cell line named NB4 cells. This induction of autophagy is associated with downregulation of Bcl-2 and inhibition of mTOR activity. Small interfering RN A-mediated knockdown of BECN1 expression enhances apoptosis triggered by ATRA in NB4 cells but does not affect the differentiation process. These results provide evidence that the upregulation of Beclin 1 by ATRA constitutes an anti-apoptotic signal for maintaining the viability of mature APL cells, but has no crucial effect on the granulocytic differentiation. This finding may help to elucidate the mechanisms involved in ATRA resistance of APL patients, and in the ATRA syndrome caused by an accumulation of mature APL cells.",
keywords = "APL, ATRA, Apoptosis, Autophagy, Beclin 1, Differentiation",
author = "Aurore Trocoli and Julie Mathieu and Muriel Priault and Josy Reiffers and Sylvie Souquere and G{\'e}rard Pierron and Fran{\c c}oise Besan{\c c}on and Mojgan Djavaheri-Mergny",
note = "Funding Information: microscope at 80 kV in ultrathin sections stained with uranyl This work was supported by funds from the Institut National de acetate and lead citrate. la Sant{\'e} et de la Recherche M{\'e}dicale (INSERM), the University Protein gel blot analysis. Cell extracts were prepared in of Bordeaux and IFR 66, as well as by a grant from Ligue contre 10 mM Tris, pH 7.4, 1% SDS, 1 mM sodium vanadate, treated le Cancer comit{\'e} de la Gironde and by a regional administration with benzonase nuclease for 5 min at room temperature, and grant from R{\'e}gion Aquitain. A.T. is supported by a Ph.D. fellow-boiled for 3 min. Fractions (30–50 μg) of cellular extract pro-ship from the Conseil R{\'e}gional Aquitaine/INSERM. We thank teins were subjected to SDS-PAGE using a Tris/glycine buffer Ga{\"e}lle Labrunie for her technical support and Pippa McKelvie-system based on the method of Laemmli. After electrophoresis, Sebileau for help with the English editing.",
year = "2011",
month = jan,
day = "1",
doi = "10.4161/auto.7.10.16623",
language = "English",
volume = "7",
pages = "1108--1114",
journal = "Autophagy",
issn = "1554-8627",
number = "10",
}