title: Efflux transporter mRNA expression profiles in differentiating JEG-3 human choriocarcinoma cells as a placental transport model.
abstract: The kinetics of drug transport across the trophoblast layer is determined by several factors. Human choriocarcinoma cell lines like BeWo and JEG-3 have been used as models of the trophoblast layer to examine the placental transport of drugs. Previously, the drugs examined in these models have been readily transported across the trophoblast layer via cellular gap junctions. These backgrounds enabled us to establish the differentiating JEG-3 cell (DJEG) layer model, which suppresses paracellular drug transport, as an evaluation system of placental drug transport. The efflux transporters on the trophoblast layer assume the meaningful role of protecting the fetus from xenobiotic substances. In order to clarify the usefulness of our DJEG placental drug transport model, this study examined the mRNA expression profiles of the efflux transporters MRPs, MDR1, and BCRP in JEG-3 cells and compared them with those of BeWo cells and their known placental expression. We suggest that the mRNA of efflux transporters MRP 1-8 and BCRP are expressed widely in JEG-3 cells; however, expression levels of MDR1 mRNA were undetectable. It was also indicated that polymorphisms of BCRP C421A in both the BeWo and JEG-3 cells are of the wild-type. We demonstrated the efflux transporters' expression profiles, as well as those of the BeWo cells, was demonstrated in the DJEG placental drug transport evaluating model as well as the BeWo cells, in the DJEG placental drug transport evaluation model. Based on these findings, we hope that the DJEG model will be adequate for use in evaluating placental drug transport in relation to the transporter proteins.
authors.affiliation: Laboratory of Clinical Pharmaceutics, Faculty of Pharmacy, Osaka Ohtani University, Yao Municipal Hospital, Tondabayashi city, Osaka, Japan. ikedak@osaka-ohtani.ac.jp
authors.forename: K
authors.initials: K
authors.lastname: Ikeda
authors.forename: K
authors.initials: K
authors.lastname: Yamasaki
authors.forename: M
authors.initials: M
authors.lastname: Homemoto
authors.forename: S
authors.initials: S
authors.lastname: Yamaue
authors.forename: M
authors.initials: M
authors.lastname: Ogawa
authors.forename: E
authors.initials: E
authors.lastname: Nakao
authors.forename: Y
authors.initials: Y
authors.lastname: Fukunaga
authors.forename: T
authors.initials: T
authors.lastname: Nakanishi
authors.forename: N
authors.initials: N
authors.lastname: Utoguchi
authors.forename: M
authors.initials: M
authors.lastname: Myotoku
authors.forename: Y
authors.initials: Y
authors.lastname: Hirotani
mesh_terms: D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters / Q000378:metabolism; D001693:Biological Transport, Active; D018938:Caco-2 Cells; D002454:Cell Differentiation / Q000502:physiology; D045744:Cell Line, Tumor; D002822:Choriocarcinoma / Q000235:genetics / Q000378:metabolism*; D062445:Claudin-1; D017931:DNA Primers; D005260:Female; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics; D026901:Membrane Transport Proteins / Q000096:biosynthesis* / Q000235:genetics*; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000235:genetics; D009363:Neoplasm Proteins / Q000378:metabolism; D004364:Pharmaceutical Preparations / Q000378:metabolism*; D010920:Placenta / Q000378:metabolism*; D011110:Polymorphism, Genetic / Q000235:genetics; D011247:Pregnancy; D012333:RNA, Messenger / Q000096:biosynthesis* / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D019108:Tight Junctions / Q000378:metabolism; D014594:Uterine Neoplasms / Q000235:genetics / Q000378:metabolism*
chemical_list: D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters; D062445:Claudin-1; D017931:DNA Primers; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D009363:Neoplasm Proteins; D004364:Pharmaceutical Preparations; D012333:RNA, Messenger; C116614:ABCG2 protein, human; C568108:CLDN1 protein, human