Regulation of myeloblastin messenger RNA expression in myeloid leukemia cells treated with all-trans retinoic acid.
Retinoic acid is known to induce differentiation of human myeloid leukemia cells in vitro. Recently, all-trans retinoic acid has been used to induce remissions in patients with acute promyelocytic leukemia, probably through differentiation of the leukemia cells. Myeloblastin (mbn) is a protease that has been identified in the human leukemia cell line HL-60. Downregulation of this protease can inhibit proliferation and induce differentiation of HL-60-derived leukemia cells. Here we have investigated the regulation of mbn messenger RNA (mRNA) expression in two human leukemia cell lines, HL-60 and NB4, treated with all-trans retinoic acid. Under this treatment, downregulation of mbn mRNA was observed in both cell lines, but was considerably delayed in NB4 cells that carry the t(15;17) translocation characteristic of acute promyelocytic leukemia. We have found that multiple mechanisms were involved in the control of mbn mRNA expression. These mechanisms were different in HL-60 and NB4 cells. Our results show that in HL-60 cells, all-trans retinoic acid rapidly decreased transcription of mbn. In contrast, in the t(15;17)-positive NB4 cells treated with all-trans retinoic acid, upregulation of mbn mRNA expression was followed by a late downregulation, both achieved via posttranscriptional mechanisms.
Labbaye
C
C
Department of Physiology, Columbia University College of Physicians and Surgeons, New York, NY 10032.
Zhang
J
J
Casanova
J L
JL
Lanotte
M
M
Teng
J
J
Miller
W H
WH
Cayre
Y E
YE
D002453:Cell Cycle / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D002884:Chromosomes, Human, Pair 15; D002886:Chromosomes, Human, Pair 17; D003513:Cycloheximide / Q000494:pharmacology; D003609:Dactinomycin / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D007951:Leukemia, Myeloid; D015473:Leukemia, Promyelocytic, Acute; D053146:Myeloblastin; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D012334:RNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D012697:Serine Endopeptidases / Q000235:genetics*; D013997:Time Factors; D014158:Transcription, Genetic / Q000187:drug effects; D014178:Translocation, Genetic; D014212:Tretinoin / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D012333:RNA, Messenger; D012334:RNA, Neoplasm; D003609:Dactinomycin; D014212:Tretinoin; D003513:Cycloheximide; D012697:Serine Endopeptidases; D053146:Myeloblastin