Genomic structure, gene expression, and promoter analysis of human multidrug resistance-associated protein 7.
The multidrug resistance-associated protein (MRP) subfamily transporters associated with anticancer drug efflux are attributed to the multidrug-resistance of cancer cells. The genomic organization of human multidrug resistance-associated protein 7 (MRP7) was identified. The human MRP7 gene, consisting of 22 exons and 21 introns, greatly differs from other members of the human MRP subfamily. A splicing variant of human MRP7, MRP7A, expressed in most human tissues, was also characterized. The 1.93-kb promoter region of MRP7 was isolated and shown to support luciferase activity at a level 4- to 5-fold greater than that of the SV40 promoter. Basal MRP7 gene expression was regulated by 2 regions in the 5'-flanking region at -1,780-1,287 bp, and at -611 to -208 bp. In Madin-Darby canine kidney (MDCK) cells, MRP7 promoter activity was increased by 226% by genotoxic 2-acetylaminofluorene and 347% by the histone deacetylase inhibitor, trichostatin A. The protein was expressed in the membrane fraction of transfected MDCK cells.
Kao
Hsin-hsin
HH
Department of Food Nutrition, Chung-Hwa College of Medical Technology, Tainan, Taiwan, ROC.
Chang
Ming-shi
MS
Cheng
Jan-fang
JF
Huang
Jin-ding
JD
D015073:2-Acetylaminofluorene / Q000494:pharmacology; D020121:5' Untranslated Regions / Q000235:genetics; D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D018076:DNA, Complementary / Q000302:isolation & purification; D004285:Dogs; D005786:Gene Expression Regulation / Q000187:drug effects*; D016678:Genome; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology; D008969:Molecular Sequence Data; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000096:biosynthesis / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D020033:Protein Isoforms / Q000096:biosynthesis / Q000235:genetics; D014162:Transfection
D015073:2-Acetylaminofluorene; D020121:5' Untranslated Regions; D018076:DNA, Complementary; D006877:Hydroxamic Acids; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D020033:Protein Isoforms; C421142:ABCC10 protein, human; C012589:trichostatin A