RETINOID-REGULATED EXPRESSION OF BCL-2 AND TISSUE TRANSGLUTAMINASE DURING THE DIFFERENTIATION AND APOPTOSIS OF HUMAN MYELOID-LEUKEMIA (HL-60) CELLS

Retinoids induce terminal differentiation and subsequent apoptosis in the human myeloid leukemia (HL-60) cell line. We have previously shown that in HL-60 cells, ligand activation of retinoic acid receptors (RA Rs) is sufficient to induce differentiation but ligand activation of r etinoid X receptors (RXRs) is necessary for the retinoid-induced apopt osis of these cells. In the present studies we have characterized the effect of retinoids on the expression of two apoptosis-linked gene pro ducts, BCL-2 and tissue transglutaminase. BCL-2 is a membrane-associat ed protein whose expression has been linked to the suppression of apop tosis in many cells. Tissue transglutaminase is a protein cross-linkin g enzyme that accumulates in many cells undergoing apoptotic cell deat h. Our data suggest that ligand activation of RARs in HL-60 cells resu lts in a global suppression of BCL-2 expression whereas ligand activat ion of both RARs and RXRs triggers the selective accumulation of tissu e transglutaminase in the apoptotic HL-60 cells. Copyright (C) 1996 El sevier Science Ltd.