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The role of RAR and RXR activation in retinoid-induced tissue factor suppression
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. (Coagulation Research)
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
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2000 (English)In: Leukemia, ISSN 0887-6924, E-ISSN 1476-5551, Vol. 14, no 6, 1105-11 p.Article in journal (Refereed) Published
Abstract [en]

Excessive expression of tissue factor (TF) is a common finding in leukaemic cells and may contribute to thrombotic complications in patients. Retinoic acid has been shown to induce differentiation and reduce TF expression in acute promyelocytic leukaemia (APL) cells in vitro, and to induce remission in APL patients. Treatment of the APL cell line NB4 with the specific retinoic acid receptor-alpha (RARalpha) agonists Ro4-6055 or TTNPB resulted in down-regulation of TF expression and in induction of differentiation. The activation of RARbeta, RARgamma or retinoid X receptor (RXR) did not suppress the constitutive TF expression in NB4 cells. Moreover, the RARalpha antagonist Ro41-5253 blocked the retinoid-induced down-regulation of TF. In contrast, in the monoblastic U-937 cell line only a partial suppression of TF antigen expression and activity was observed by treatment with the RAR agonist TTNPB or the RXR agonist SR11237 alone. However, the combination of TTNPB and SR11237 resulted in a pronounced down-regulation of TF expression and induction of differentiation in U-937 cells. We show for the first time that the activation of both subunits of the RARalpha-RXR transcriptional complex is needed for TF suppression in U-937 cells, whereas in NB4 cells RARalpha activation alone is sufficient. Thus, distinct molecular mechanisms for TF suppression seem to be operating in leukaemic cell lines of different origin.

Place, publisher, year, edition, pages
2000. Vol. 14, no 6, 1105-11 p.
Keyword [en]
tissue factor, RAR, RXR, differentiation
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:uu:diva-51408PubMedID: 10865976OAI: oai:DiVA.org:uu-51408DiVA: diva2:79317
Available from: 2008-10-17 Created: 2008-10-17 Last updated: 2017-12-04Bibliographically approved

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Botling, JohanÖberg, FredrikNilsson, Kenneth

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