[Effects of 9-cis retinoic acid on hematopoiesis in vitro].
9-cis retinoic acid (cRA) is a high affinity ligand for RXR and binds efficiently to RAR. cRA in general was more potent than all-trans RA (tRA) in suppressing clonal growth and inducing differentiation of HL-60 and human leukemic cells. At very low concentrations, retinoid stimulate proliferation of leukemic cells rather than induce their differentiation. Also, cRA in combination with tRA could induce differentiation of RA resistant HL-60 cells. Steady-state levels of RAR-alpha mRNA in HL-60 cells were not affected by either cRA or tRA. In contrast, cRA, but not tRA could reduced RXR-alpha mRNA accumulation in dose-dependent manner. The loss of partner for RAR may result in differential gene regulation through the retinoid pathway. These differences in regulation of RAR and RXR mRNA might be of physiological significance.
Kizaki
M
M
Division of Hematology, Keio University School of Medicine.
Nakajima
H
H
Ikeda
Y
Y
D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D006410:Hematopoiesis / Q000187:drug effects*; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics; D018168:Receptors, Retinoic Acid; D047488:Retinoid X Receptors; D014157:Transcription Factors; D014212:Tretinoin / Q000494:pharmacology*; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000473:pathology
D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; D018168:Receptors, Retinoic Acid; D047488:Retinoid X Receptors; D014157:Transcription Factors; D014212:Tretinoin