title: C-myc amplification altered the gene expression of ABC- and SLC-transporters in human breast epithelial cells.
abstract: The present study aimed to investigate the effect of c-Myc overexpression on the gene expression and functional activity of major drug transporters in breast epithelial cells. In order to reflect c-Myc overexpressed epithelial cells, MCF10A cells (human mammary epithelial cells) stably expressing c-Myc (c-Myc-MCF10A cells) have been established by retroviral infection and then the effect of c-Myc activation on the gene expression and functional activity of 16 influx and efflux transporters was examined in c-Myc-MCF10A cells. In RT-PCR analysis, the quantitative difference in transporters' gene expression profiles was observed after c-Myc activation. Western blot analysis also indicated that the protein expression of some transporters (MCT1, OCT1, MRP1, MRP2 and BCRP) increased by c-Myc overexpression. In parallel to the alteration in gene expression, functional activity studies indicated that the cellular uptake of benzoic acid, MPP+, calcein-AM, H33342, representative substrates of MCT1, OCT1, MRPs and BCRP, respectively, was significantly (p < 0.05) altered by c-Myc overexpression. In conclusion, c-Myc amplification appeared to be coupled with the modulation of gene expression of certain drug transporters in human breast epithelial cells.
authors.affiliation: BK21 Project Team, College ofPharmacy, Chosun University, Gwangju, Korea.
authors.forename: Keon Wook
authors.initials: KW
authors.lastname: Kang
authors.forename: Young Bin
authors.initials: YB
authors.lastname: Im
authors.forename: Woon-Jung
authors.initials: WJ
authors.lastname: Go
authors.forename: Hyo-Kyung
authors.initials: HK
authors.lastname: Han
mesh_terms: D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters / Q000235:genetics*; D001562:Benzimidazoles / Q000378:metabolism; D001565:Benzoates / Q000378:metabolism; D015153:Blotting, Western; D001940:Breast / Q000166:cytology / Q000378:metabolism*; D002478:Cells, Cultured; D005260:Female; D005452:Fluoresceins / Q000378:metabolism; D005784:Gene Amplification; D006801:Humans; D027501:Monocarboxylic Acid Transporters / Q000235:genetics* / Q000378:metabolism; D000089762:Multidrug Resistance-Associated Protein 2; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000235:genetics* / Q000378:metabolism; D009363:Neoplasm Proteins / Q000235:genetics*; D050811:Octamer Transcription Factor-1 / Q000235:genetics* / Q000378:metabolism; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D027981:Symporters / Q000235:genetics* / Q000378:metabolism; D000099233:Monocarboxylate Transport Protein 1
chemical_list: D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters; D001562:Benzimidazoles; D001565:Benzoates; D005452:Fluoresceins; D027501:Monocarboxylic Acid Transporters; D000089762:Multidrug Resistance-Associated Protein 2; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D009363:Neoplasm Proteins; D050811:Octamer Transcription Factor-1; D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger; D027981:Symporters; D000099233:Monocarboxylate Transport Protein 1; C000715087:ABCC2 protein, human; C116614:ABCG2 protein, human; C489427:MYC protein, human; C494165:POU2F1 protein, human; C085925:calcein AM; C017807:bisbenzimide ethoxide trihydrochloride; C421109:multidrug resistance-associated protein 1