Cell Growth & Differentiation, Vol 7, Issue 2 179-186, Copyright © 1996 by American Association of Cancer Research

ARTICLES

Activation of retinoid receptors RAR alpha and RXR alpha induces differentiation and apoptosis, respectively, in HL-60 cells

K Mehta, T McQueen, N Neamati, S Collins and M Andreeff
Department of Bioimmunotherapy, University of Texas M.D. Anderson Cancer Center, Houston 77030, USA.

Induction of granulocytic differentiation in HL-60 myeloid leukemia cells by retinoids is followed by their death via apoptosis. Retinoids are known to mediate their biological effects through at least two distinct types of nuclear receptors, the retinoic acid receptors and retinoid X receptors. We undertook to characterize the potential role of these receptors in inducing differentiation and apoptosis by retinoids. For this, we used a previously described variant of an HL-60 cell line (HL-60R) in which retinoid receptor function has been abrogated due to a trans-dominant negative mutation. Retroviral vector-mediated gene transfer was used to introduce the normal retinoic acid receptor (RAR alpha) or retinoid X receptor (RXR alpha) into HL-60R cells. Our results suggest that ligand-induced activation of RAR alpha is sufficient to induce differentiation in HL-60 cells, whereas activation of RXR alpha can induce direct apoptosis of these cells without their prior commitment to differentiate.

This article has been cited by other articles:

				S. Taschner, C. Koesters, B. Platzer, A. Jorgl, W. Ellmeier, T. Benesch, and H. Strobl Down-regulation of RXR{alpha} expression is essential for neutrophil development from granulocyte/monocyte progenitors Blood, February 1, 2007; 109(3): 971 - 979. [Abstract] [Full Text] [PDF]

				R. Lambrot, H. Coffigny, C. Pairault, A.-C. Donnadieu, R. Frydman, R. Habert, and V. Rouiller-Fabre Use of Organ Culture to Study the Human Fetal Testis Development: Effect of Retinoic Acid J. Clin. Endocrinol. Metab., July 1, 2006; 91(7): 2696 - 2703. [Abstract] [Full Text] [PDF]

				V. Van Merris, E. Meyer, L. Duchateau, and C. Burvenich Differential Effects of Steroids and Retinoids on Bovine Myelopoiesis in Vitro J Dairy Sci, May 1, 2004; 87(5): 1188 - 1195. [Abstract] [Full Text] [PDF]

				T. Kuwata, I-M. Wang, T. Tamura, R. M. Ponnamperuma, R. Levine, K. L. Holmes, H. C. Morse III, L. M. De Luca, and K. Ozato Vitamin A deficiency in mice causes a systemic expansion of myeloid cells Blood, June 1, 2000; 95(11): 3349 - 3356. [Abstract] [Full Text] [PDF]

				G. Livera, V. Rouiller-Fabre, P. Durand, and R. Habert Multiple Effects of Retinoids on the Development of Sertoli, Germ, and Leydig Cells of Fetal and Neonatal Rat Testis in Culture Biol Reprod, May 1, 2000; 62(5): 1303 - 1314. [Abstract] [Full Text]

				K. W. Braun, W. A. Tribley, M. D. Griswold, and K. H. Kim Follicle-stimulating Hormone Inhibits All-trans-retinoic Acid-induced Retinoic Acid Receptor alpha Nuclear Localization and Transcriptional Activation in Mouse Sertoli Cell Lines J. Biol. Chem., February 11, 2000; 275(6): 4145 - 4151. [Abstract] [Full Text] [PDF]

				B. Boulogne, C. Levacher, P. Durand, and R. Habert Retinoic Acid Receptors and Retinoid X Receptors in the Rat Testis During Fetal and Postnatal Development: Immunolocalization and Implication in the Control of the Number of Gonocytes Biol Reprod, December 1, 1999; 61(6): 1548 - 1557. [Abstract] [Full Text]

				H. Wan, M. I. Dawson, W. K. Hong, and R. Lotan Overexpressed Activated Retinoid X Receptors Can Mediate Growth Inhibitory Effects of Retinoids in Human Carcinoma Cells J. Biol. Chem., October 9, 1998; 273(41): 26915 - 26922. [Abstract] [Full Text] [PDF]

				K. M. Akmal, J. M. Dufour, M. Vo, S. Higginson, and K. H. Kim Ligand-Dependent Regulation of Retinoic Acid Receptor {alpha} in Rat Testis: In Vivo Response to Depletion and Repletion of Vitamin A Endocrinology, March 1, 1998; 139(3): 1239 - 1248. [Abstract] [Full Text] [PDF]

				Y. Monczak, M. Trudel, W. W. Lamph, and W. H. Miller Jr Induction of Apoptosis Without Differentiation by Retinoic Acid in PLB-985 Cells Requires the Activation of Both RAR and RXR Blood, November 1, 1997; 90(9): 3345 - 3355. [Abstract] [Full Text] [PDF]

				K. Mehta, T. McQueen, T. Manshouri, M. Andreeff, S. Collins, and M. Albitar Involvement of Retinoic Acid Receptor-alpha -Mediated Signaling Pathway in Induction of CD38 Cell-Surface Antigen Blood, May 15, 1997; 89(10): 3607 - 3614. [Abstract] [Full Text] [PDF]