title: PPARα and PPARγ regulate the nucleoside transporter hENT1.
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. PPARα and PPARγ agonists, Wy14,643 and RGZ, increased hENT1 expression, but only PPARα 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 PPARα-but not PPARγ-mediated expression regulation of hENT1 is PPRE-dependent. In conclusion, PPARα and PPARγ activation modulate hENT1 expression.
authors.affiliation: Department of Hematology-Oncology, School of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile.
authors.forename: Trinidad D
authors.initials: TD
authors.lastname: Montero
authors.forename: Dusan
authors.initials: D
authors.lastname: Racordon
authors.forename: Loreto
authors.initials: L
authors.lastname: Bravo
authors.forename: Gareth I
authors.initials: GI
authors.lastname: Owen
authors.forename: Miguel L
authors.initials: ML
authors.lastname: Bronfman
authors.forename: Andrea V
authors.initials: AV
authors.lastname: Leisewitz
mesh_terms: D002460:Cell Line; D033721:Equilibrative Nucleoside Transporter 1 / Q000235:genetics*; D005786:Gene Expression Regulation; D006801:Humans; D047493:PPAR alpha / Q000819:agonists / Q000378:metabolism*; D047495:PPAR gamma / Q000819:agonists / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D011743:Pyrimidines / Q000494:pharmacology; D014162:Transfection; D015854:Up-Regulation
chemical_list: D033721:Equilibrative Nucleoside Transporter 1; D047493:PPAR alpha; D047495:PPAR gamma; D011743:Pyrimidines; C438649:SLC29A1 protein, human; C006253:pirinixic acid