C-myc amplification altered the gene expression of ABC- and SLC-transporters in human breast epithelial cells.
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.
Kang
Keon Wook
KW
BK21 Project Team, College ofPharmacy, Chosun University, Gwangju, Korea.
Im
Young Bin
YB
Go
Woon-Jung
WJ
Han
Hyo-Kyung
HK
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
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