Activation of retinoid receptors RARα and RXRα induces differentiation and apoptosis, respectively, in HL-60 cells

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 (RARα) or retinoid X receptor (RXRα) into HL-60R cells. Our results suggest that ligand-induced activation of RARα is sufficient to induce differentiation in HL-60 cells, whereas activation of RXRα can induce direct apoptosis of these cells without their prior commitment to differentiate.