Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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ADP-ribosyl Cyclase
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ADP-ribosyl Cyclase 1
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Antigens, CD / drug effects
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Antigens, CD / genetics
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Antigens, CD / metabolism
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Antigens, Differentiation / drug effects
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Antigens, Differentiation / genetics
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Antigens, Differentiation / metabolism
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Apoptosis / drug effects
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Apoptosis / physiology
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Cell Differentiation / drug effects
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Cell Differentiation / physiology
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DNA / analysis
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DNA-Binding Proteins / agonists
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DNA-Binding Proteins / physiology*
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Gene Expression / drug effects
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Gene Expression / physiology
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HL-60 Cells / cytology*
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HL-60 Cells / physiology
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HL-60 Cells / ultrastructure
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Humans
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In Situ Hybridization
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Membrane Glycoproteins
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Mutation / physiology
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N-Glycosyl Hydrolases / drug effects
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N-Glycosyl Hydrolases / genetics
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N-Glycosyl Hydrolases / metabolism
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Receptors, Retinoic Acid / agonists
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Receptors, Retinoic Acid / physiology*
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Retinoic Acid Receptor alpha
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Retinoid X Receptors
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Signal Transduction / physiology
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Transcription Factors / agonists
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Transcription Factors / physiology*
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Transglutaminases / drug effects
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Transglutaminases / genetics
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Transglutaminases / metabolism
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Tretinoin / pharmacology
Substances
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Antigens, CD
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Antigens, Differentiation
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DNA-Binding Proteins
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Membrane Glycoproteins
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RARA protein, human
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Receptors, Retinoic Acid
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Retinoic Acid Receptor alpha
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Retinoid X Receptors
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Transcription Factors
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Tretinoin
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DNA
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Transglutaminases
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N-Glycosyl Hydrolases
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ADP-ribosyl Cyclase
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CD38 protein, human
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ADP-ribosyl Cyclase 1