Premium
Evidence that the pregnane X and retinoid receptors PXR , RAR and RXR may regulate transcription of the transporter h OCT 1 in chronic myeloid leukaemia cells
Author(s) -
Austin Gemma,
Holcroft Alison,
Rinne Natasha,
Wang Lihui,
Clark Richard E.
Publication year - 2015
Publication title -
european journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.904
H-Index - 84
eISSN - 1600-0609
pISSN - 0902-4441
DOI - 10.1111/ejh.12409
Subject(s) - pregnane x receptor , retinoid x receptor , receptor , retinoid x receptor alpha , downregulation and upregulation , nuclear receptor , chemistry , pharmacology , constitutive androstane receptor , biology , cancer research , microbiology and biotechnology , transcription factor , biochemistry , gene
The expression and activity of the uptake transporter human organic cation transporter 1 (hOCT1; SLC 22A1) is an independent predictor of response to imatinib treatment in patients with chronic myeloid leukaemia ( CML ). We have recently shown that peroxisome proliferator‐activated receptor ( PPAR ) activation can increase the killing effect of imatinib in CML cells, due to upregulated hOCT1 gene expression and increased imatinib uptake. To investigate the role of activation of nuclear receptors other than PPAR in the transcriptional regulation of hOCT1 , CML cells were treated with agonists for 13 adopted orphan receptors and endocrine receptors. It was found that hOCT1 expression was upregulated by the agonists for pregnane X receptor ( PXR ), retinoid acid receptor ( RAR ) and retinoid X receptor ( RXR ) in CML cell line and primary CML cells ( P = 0.04; Wilcoxon rank test). Hence, agonists for PXR , RAR and RXR may be potentially used to improve the efficacy of imatinib in patients with CML .