Lineage restriction of the RARalpha gene expression in myeloid differentiation.

2.50
Hdl Handle:
http://hdl.handle.net/10541/85519
Title:
Lineage restriction of the RARalpha gene expression in myeloid differentiation.
Authors:
Zhu, Jun; Heyworth, Clare M; Glasow, Annegret; Huang, Qiu-Hua; Petrie, Kevin; Lanotte, Michael; Benoit, Gerard; Gallagher, Robert; Waxman, Samuel; Enver, Tariq; Zelent, Arthur
Abstract:
To better understand the role of retinoids in myelopoiesis, expression of the retinoid receptor genes (retinoic acid receptors [RARs] and retinoid X receptors [RXRs]) were examined during differentiation of factor-dependent cell-Paterson (FDCP)-mixA4 murine progenitor cells. The major receptor expressed in undifferentiated A4 cells was RARalpha (primarily the RARalpha1 isoform). Following induction of myelomonocytic differentiation with granulocyte and granulocyte-macrophage colony-stimulating factors, a dramatic increase in RARalpha expression (particularly the RARalpha2 isoform) was seen. In contrast, expression of both RARalpha isoforms was rapidly extinguished upon induction of erythroid differentiation with erythropoeitin (EPO). A modest induction of RXRalpha expression was seen, particularly during differentiation in the myelomonocytic lineage. Low expression levels of RARgamma2 and RXRbeta remained unchanged, irrespective of differentiation pathway. Consistent with the gene expression patterns, RARalpha agonists and antagonists stimulated myelomonocytic and erythroid differentiation of FDCP-mixA4 cells, respectively. Taken together, these results suggest that erythropoiesis and granulopoiesis require diminished and enhanced RARalpha activities, respectively, which at physiological all-trans-retinoic acid (RA) concentrations may be accomplished by reciprocal effects of EPO and myelomonocytic growth factors on its expression. This hypothesis is corroborated by data showing that RA, which positively regulates RARalpha2 expression, can exert inhibitory effects on erythroid differentiation.
Affiliation:
Leukaemia Research Fund Centre and Section of Gene Function and Regulation at the Institute of Cancer Research, Chester Beatty Laboratories, London, United Kingdom.
Citation:
Lineage restriction of the RARalpha gene expression in myeloid differentiation. 2001, 98 (8):2563-7 Blood
Journal:
Blood
Issue Date:
15-Oct-2001
URI:
http://hdl.handle.net/10541/85519
PubMed ID:
11588055
Type:
Article
Language:
en
ISSN:
0006-4971
Appears in Collections:
All Paterson Institute for Cancer Research

Full metadata record

DC FieldValue Language
dc.contributor.authorZhu, Junen
dc.contributor.authorHeyworth, Clare Men
dc.contributor.authorGlasow, Annegreten
dc.contributor.authorHuang, Qiu-Huaen
dc.contributor.authorPetrie, Kevinen
dc.contributor.authorLanotte, Michaelen
dc.contributor.authorBenoit, Gerarden
dc.contributor.authorGallagher, Roberten
dc.contributor.authorWaxman, Samuelen
dc.contributor.authorEnver, Tariqen
dc.contributor.authorZelent, Arthuren
dc.date.accessioned2009-11-06T09:40:56Z-
dc.date.available2009-11-06T09:40:56Z-
dc.date.issued2001-10-15-
dc.identifier.citationLineage restriction of the RARalpha gene expression in myeloid differentiation. 2001, 98 (8):2563-7 Blooden
dc.identifier.issn0006-4971-
dc.identifier.pmid11588055-
dc.identifier.urihttp://hdl.handle.net/10541/85519-
dc.description.abstractTo better understand the role of retinoids in myelopoiesis, expression of the retinoid receptor genes (retinoic acid receptors [RARs] and retinoid X receptors [RXRs]) were examined during differentiation of factor-dependent cell-Paterson (FDCP)-mixA4 murine progenitor cells. The major receptor expressed in undifferentiated A4 cells was RARalpha (primarily the RARalpha1 isoform). Following induction of myelomonocytic differentiation with granulocyte and granulocyte-macrophage colony-stimulating factors, a dramatic increase in RARalpha expression (particularly the RARalpha2 isoform) was seen. In contrast, expression of both RARalpha isoforms was rapidly extinguished upon induction of erythroid differentiation with erythropoeitin (EPO). A modest induction of RXRalpha expression was seen, particularly during differentiation in the myelomonocytic lineage. Low expression levels of RARgamma2 and RXRbeta remained unchanged, irrespective of differentiation pathway. Consistent with the gene expression patterns, RARalpha agonists and antagonists stimulated myelomonocytic and erythroid differentiation of FDCP-mixA4 cells, respectively. Taken together, these results suggest that erythropoiesis and granulopoiesis require diminished and enhanced RARalpha activities, respectively, which at physiological all-trans-retinoic acid (RA) concentrations may be accomplished by reciprocal effects of EPO and myelomonocytic growth factors on its expression. This hypothesis is corroborated by data showing that RA, which positively regulates RARalpha2 expression, can exert inhibitory effects on erythroid differentiation.en
dc.language.isoenen
dc.subjectLeukaemiaen
dc.subjectCultured Tumour Cellsen
dc.subjectHaematopoietic Stem Cellsen
dc.subject.meshBone Marrow-
dc.subject.meshBone Marrow Cells-
dc.subject.meshCell Differentiation-
dc.subject.meshCells, Cultured-
dc.subject.meshDNA Primers-
dc.subject.meshErythropoietin-
dc.subject.meshGene Expression Regulation-
dc.subject.meshGranulocyte Colony-Stimulating Factor-
dc.subject.meshGranulocyte-Macrophage Colony-Stimulating Factor-
dc.subject.meshHL-60 Cells-
dc.subject.meshHematopoietic Stem Cells-
dc.subject.meshHumans-
dc.subject.meshLeukemia-
dc.subject.meshModels, Biological-
dc.subject.meshReceptors, Retinoic Acid-
dc.subject.meshReverse Transcriptase Polymerase Chain Reaction-
dc.subject.meshTretinoin-
dc.subject.meshTumor Cells, Cultured-
dc.titleLineage restriction of the RARalpha gene expression in myeloid differentiation.en
dc.typeArticleen
dc.contributor.departmentLeukaemia Research Fund Centre and Section of Gene Function and Regulation at the Institute of Cancer Research, Chester Beatty Laboratories, London, United Kingdom.en
dc.identifier.journalBlooden
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