PPAR alpha and PPAR gamma regulate the nucleoside transporter hENT1
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Date
2012
Journal Title
Journal ISSN
Volume Title
Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
Abstract
Human equilibrative nucleoside transporter 1 (hENT1) is an important determinant for nucleoside analog based chemotherapy success. Preliminary data suggest hENT1 regulation by PPARs. Using A2780 cells, we investigated the role of PPARs on hENT1 expression and activity.
PPAR alpha and PPAR gamma agonists, Wy14,643 and RGZ, increased hENT1 expression, but only PPAR alpha activation or overexpression resulted in higher hENT1 transport activity. On the other hand, promoter analysis showed two putative PPRE in hENT1 promoter and luciferase-coupled promoter constructs were generated and analyzed. Our results suggest that PPAR alpha-but not PPAR gamma-mediated expression regulation of hENT1 is PPRE-dependent. In conclusion, PPAR alpha and PPAR gamma activation modulate hENT1 expression. (C) 2012 Elsevier Inc. All rights reserved.
PPAR alpha and PPAR gamma agonists, Wy14,643 and RGZ, increased hENT1 expression, but only PPAR alpha activation or overexpression resulted in higher hENT1 transport activity. On the other hand, promoter analysis showed two putative PPRE in hENT1 promoter and luciferase-coupled promoter constructs were generated and analyzed. Our results suggest that PPAR alpha-but not PPAR gamma-mediated expression regulation of hENT1 is PPRE-dependent. In conclusion, PPAR alpha and PPAR gamma activation modulate hENT1 expression. (C) 2012 Elsevier Inc. All rights reserved.
Description
Keywords
Equilibrative nucleoside transporter, PPAR alpha, Chemotherapeutic drugs, PROLIFERATOR-ACTIVATED RECEPTORS, LIPID-METABOLISM, IN-VIVO, CANCER, GEMCITABINE, MECHANISMS, CELLS, THIAZOLIDINEDIONES, DIFFERENTIATION, SENSITIVITY