Retinoic acid-induced granulocytic differentiation of HL-60 myeloid leukemia cells is mediated directly through the retinoic acid receptor (RAR-alpha).
Retinoic acid (RA) induces terminal granulocytic differentiation of the HL-60 promyelocytic leukemia cell line as well as certain other human myeloid leukemias. Specific RA receptors that are members of the steroid-thyroid hormone superfamily of nuclear transcription factors have recently been identified. We developed an HL-60 subclone that was relatively resistant to RA-induced differentiation. Specific nuclear RA receptors in this RA-resistant subclone had a decreased affinity for RA and exhibited a lower molecular weight compared with nuclear RA receptors from the RA-sensitive parental HL-60 cells. Retroviral vector-mediated transduction of a single copy of the RA receptor (RAR-alpha) into this RA-resistant HL-60 subclone restored the sensitivity of these cells to RA. These observations indicate that RAR-alpha plays a critical and central role in mediating RA-induced terminal differentiation of HL-60 leukemia cells.
Collins
S J
SJ
Molecular Medicine Program, Fred Hutchinson Cancer Research Center, Seattle, Washington 98104.
Robertson
K A
KA
Mueller
L
L
D018821:CD18 Antigens; D002352:Carrier Proteins / Q000502:physiology*; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D006098:Granulocytes / Q000166:cytology*; D006801:Humans; D066298:In Vitro Techniques; D009154:Mutation; D011518:Proto-Oncogene Proteins / Q000235:genetics; D016271:Proto-Oncogene Proteins c-myc; D016028:Receptors, Leukocyte-Adhesion / Q000235:genetics; D018168:Receptors, Retinoic Acid; D014162:Transfection; D014212:Tretinoin / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D018821:CD18 Antigens; D002352:Carrier Proteins; D011518:Proto-Oncogene Proteins; D016271:Proto-Oncogene Proteins c-myc; D016028:Receptors, Leukocyte-Adhesion; D018168:Receptors, Retinoic Acid; D014212:Tretinoin