title: Regulation of the placental BCRP transporter by PPAR gamma.
abstract: Identifying regulators of placental breast cancer resistance protein (BCRP) expression is critical as downregulation of this transporter may increase exposure of the fetus to xenobiotics. Here, we sought to test whether the nuclear receptor peroxisome proliferator-activated receptor γ (PPARγ) regulates BCRP expression in the placenta. To test this, human BeWo placental choriocarcinoma cells were cultured with the PPARγ agonist rosiglitazone or the PPARγ antagonist T0070907 for 24 h. Messenger RNA (mRNA) expression of syncytialization markers, GCM1 and hCGβ, as well as BCRP increased with PPARγ agonist treatment. Conversely, BCRP mRNA and protein expression decreased 30%-50% with PPARγ antagonist treatment. Rosiglitazone enhanced BCRP protein expression and transport activity, resulting in a 20% greater efflux of the substrate Hoechst 33342 compared with control cells. These results suggest that PPARγ can upregulate BCRP expression in the placenta, which may be important in understanding mechanisms that protect the fetus from xenobiotic exposure during development.
authors.affiliation: Rutgers University Ernest Mario School of Pharmacy, Department of Pharmacology and Toxicology, Piscataway, NJ, 08854, USA.
authors.forename: Yixin
authors.initials: Y
authors.lastname: Lin
authors.affiliation: Rutgers University Ernest Mario School of Pharmacy, Department of Pharmacology and Toxicology, Piscataway, NJ, 08854, USA.
authors.forename: Kristin M
authors.initials: KM
authors.lastname: Bircsak
authors.affiliation: Rutgers University Ernest Mario School of Pharmacy, Department of Pharmacology and Toxicology, Piscataway, NJ, 08854, USA.
authors.forename: Ludwik
authors.initials: L
authors.lastname: Gorczyca
authors.affiliation: Rutgers University Ernest Mario School of Pharmacy, Department of Pharmacology and Toxicology, Piscataway, NJ, 08854, USA.
authors.forename: Xia
authors.initials: X
authors.lastname: Wen
authors.affiliation: Rutgers University Ernest Mario School of Pharmacy, Department of Pharmacology and Toxicology, Piscataway, NJ, 08854, USA.|Environmental and Occupational Health Sciences Institute, Piscataway, NJ, 08854, USA.
authors.forename: Lauren M
authors.initials: LM
authors.lastname: Aleksunes
mesh_terms: D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2 / Q000096:biosynthesis*; D001549:Benzamides / Q000494:pharmacology; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D009363:Neoplasm Proteins / Q000096:biosynthesis*; D047495:PPAR gamma / Q000378:metabolism*; D010920:Placenta; D011247:Pregnancy; D011257:Pregnancy Proteins / Q000096:biosynthesis*; D011725:Pyridines / Q000494:pharmacology; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000494:pharmacology; D015854:Up-Regulation
chemical_list: C116614:ABCG2 protein, human; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D001549:Benzamides; D009363:Neoplasm Proteins; D047495:PPAR gamma; D011257:Pregnancy Proteins; D011725:Pyridines; C458508:T 0070907; D045162:Thiazolidinediones; D000077154:Rosiglitazone
keywords: ABCG2; BCRP; PPAR gamma; placenta; trophoblast