Austin, Gemma;
Holcroft, Alison;
Rinne, Natasha;
Wang, Lihui;
Clark, Richard E.
Evidence that the pregnane X and retinoid receptors PXR, RAR and RXR may regulate transcription of the transporter hOCT1 in chronic myeloid leukaemia cells
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Media type:
E-Article
Title:
Evidence that the pregnane X and retinoid receptors PXR, RAR and RXR may regulate transcription of the transporter hOCT1 in chronic myeloid leukaemia cells
Contributor:
Austin, Gemma;
Holcroft, Alison;
Rinne, Natasha;
Wang, Lihui;
Clark, Richard E.
imprint:
Wiley, 2015
Published in:
European Journal of Haematology, 94 (2015) 1, Seite 74-78
Description:
<jats:title>Abstract</jats:title><jats:p>The expression and activity of the uptake transporter human organic cation transporter 1 (hOCT1; <jats:styled-content style="fixed-case">SLC</jats:styled-content>22A1) is an independent predictor of response to imatinib treatment in patients with chronic myeloid leukaemia (<jats:styled-content style="fixed-case">CML</jats:styled-content>). We have recently shown that peroxisome proliferator‐activated receptor (<jats:styled-content style="fixed-case">PPAR</jats:styled-content>) activation can increase the killing effect of imatinib in <jats:styled-content style="fixed-case">CML</jats:styled-content> cells, due to upregulated hOCT1 gene expression and increased imatinib uptake. To investigate the role of activation of nuclear receptors other than <jats:styled-content style="fixed-case">PPAR</jats:styled-content> in the transcriptional regulation of <jats:italic>hOCT1</jats:italic>,<jats:styled-content style="fixed-case"> CML</jats:styled-content> cells were treated with agonists for 13 adopted orphan receptors and endocrine receptors. It was found that <jats:italic>hOCT1</jats:italic> expression was upregulated by the agonists for pregnane X receptor (<jats:styled-content style="fixed-case">PXR</jats:styled-content>), retinoid acid receptor (<jats:styled-content style="fixed-case">RAR</jats:styled-content>) and retinoid X receptor (<jats:styled-content style="fixed-case">RXR</jats:styled-content>) in <jats:styled-content style="fixed-case">CML</jats:styled-content> cell line and primary <jats:styled-content style="fixed-case">CML</jats:styled-content> cells (<jats:italic>P</jats:italic> = 0.04; Wilcoxon rank test). Hence, agonists for <jats:styled-content style="fixed-case">PXR</jats:styled-content>,<jats:styled-content style="fixed-case"> RAR</jats:styled-content> and <jats:styled-content style="fixed-case">RXR</jats:styled-content> may be potentially used to improve the efficacy of imatinib in patients with <jats:styled-content style="fixed-case">CML</jats:styled-content>.</jats:p>