Estrogen regulation of transferrin gene expression in MCF-7 human breast cancer cells.
Transferrin (Tf) is an iron transport protein expressed in MCF-7 human breast cancer cells. In nuclear run-on assays, 17beta-estradiol (E2) increased the rate of Tf gene expression approximately 3-fold within 1 h after treatment and reporter gene activity was also induced in MCF-7 cells transfected with a construct containing a -3600 to +39 Tf gene promoter insert. Deletion and mutation analysis identified an E2-responsive promoter region between -811 and -762, which was GC-rich (80%) and contained two nonconsensus estrogen response elements (EREs). E2-responsiveness of this region was associated with a GGACA(N)(3)TGGCC motif (-803 to -791) which bound human estrogen receptor alpha (hERalpha) in gel mobility shift assays. In Drosophila Schneider SL-2 cells, the -811 to -752 was E2-responsive after cotransfection with hERalpha expression plasmid plus E2, whereas Sp1 protein did not induce transactivation. These studies confirm that E2 induces Tf gene expression through a nonconsensus distal ERE.
Vyhlidal
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Department of Veterinary Physiology and Pharmacology, Texas A&M University, 4466 TAMU, College Station, Texas 77843-4466, USA.
Li
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Safe
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D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism*; D024202:Electrophoretic Mobility Shift Assay; D047628:Estrogen Receptor alpha; D004967:Estrogens / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D009154:Mutation; D011401:Promoter Regions, Genetic / Q000235:genetics; D011960:Receptors, Estrogen / Q000378:metabolism; D020218:Response Elements / Q000235:genetics; D014162:Transfection; D014168:Transferrin / Q000235:genetics*; D014407:Tumor Cells, Cultured
D047628:Estrogen Receptor alpha; D004967:Estrogens; D011960:Receptors, Estrogen; D014168:Transferrin