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 (RARs) is sufficient to induce differentiation but ligand activation of retinoid X receptors (RXRs) is necessary for the retinoid-induced apoptosis of these cells. In the present studies we have characterized the effect of retinoids on the expression of two apoptosis-linked gene products, BCL-2 and tissue transglutaminase. BCL-2 is a membrane-associated protein whose expression has been linked to the suppression of apoptosis in many cells. Tissue transglutaminase is a protein cross-linking enzyme that accumulates in many cells undergoing apoptotic cell death. Our data suggest that ligand activation of RARs in HL-60 cells results in a global suppression of BCL-2 expression whereas ligand activation of both RARs and RXRs triggers the selective accumulation of tissue transglutaminase in the apoptotic HL-60 cells.
Nagy
L
L
Department of Pharmacology, University of Texas-Houston Medical School 77225, USA.
Thomázy
V A
VA
Chandraratna
R A
RA
Heyman
R A
RA
Davies
P J
PJ
D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D015536:Down-Regulation / Q000187:drug effects; D018922:HL-60 Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D015474:Isotretinoin / Q000494:pharmacology*; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2; D018168:Receptors, Retinoic Acid / Q000502:physiology; D047488:Retinoid X Receptors; D014157:Transcription Factors / Q000502:physiology; D011503:Transglutaminases / Q000378:metabolism*; D014212:Tretinoin / Q000494:pharmacology*; D015854:Up-Regulation / Q000187:drug effects
D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D018168:Receptors, Retinoic Acid; D047488:Retinoid X Receptors; D014157:Transcription Factors; D014212:Tretinoin; D011503:Transglutaminases; D015474:Isotretinoin