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The expression of immediate early gene X-1 (IEX-1) is differentially induced by retinoic acids in NB4 and KG1 cells: possible implication in the distinct phenotype of retinoic acid-responsive and -resistant leukemic cells

Leukemia volume 18, pages 1646–1655 (2004)Cite this article

A Corrigendum to this article was published on 23 August 2006

Abstract

In a cell-type- and stimulus-dependent fashion, the early response gene immediate early gene X-1 (IEX-1) is involved in growth control and modulation of apoptosis. The present study demonstrates that, in the two acute promyelocytic leukemia (APL) cell lines NB4 and KG1, exhibiting distinct responsiveness to retinoic acids (RAs), IEX-1 expression is rapidly (30–60 min) induced by all-trans- or cis-RA and independently of other signal transduction mediators, such as TNFα, NF-κB or MAP kinases. In NB4 cells (expressing PML–RARα), this increase is transient and completely reversible, along with a cell cycle arrest, ongoing differentiation and lower sensitivity to anti-cancer-drug-induced apoptosis. In contrast, the RA-induced IEX-1 expression in KG1 cells (expressing PLZF–RARα) persists over days, along with continued cell cycle progression and increased apoptotic sensitivity. Furthermore, two functional RA-response elements in the IEX-1 promoter were identified by gel shift and luciferase reporter gene assays. IEX-1 might be a rather unique transcriptional target of the two X–RARα fusion receptors exhibiting distinct responsiveness to RAs. Following a different time course of direct transcriptional induction by PML–RARα and PLZF–RARα in NB4 and KG1 cells, respectively, IEX-1 expression may be involved in the modified actions of these receptors and the distinct phenotypes of APL cells.

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Acknowledgements

This study was supported by a grant of the German Research Society DFG (SFB-415/A13).

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  1. J Minkenberg and B Kocs: Part of a doctoral thesis

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  1. Division of Molecular Gastroenterology & Hepatology, 1st Department of Medicine, Christian-Albrechts-University, Kiel, Germany

    A Arlt, J Minkenberg, B Kocs, M Großmann, M-L Kruse, U R Fölsch & H Schäfer

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  1. A Arlt
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Correspondence to H Schäfer.

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Arlt, A., Minkenberg, J., Kocs, B. et al. The expression of immediate early gene X-1 (IEX-1) is differentially induced by retinoic acids in NB4 and KG1 cells: possible implication in the distinct phenotype of retinoic acid-responsive and -resistant leukemic cells. Leukemia 18, 1646–1655 (2004). https://doi.org/10.1038/sj.leu.2403481

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