Estradiol enhances gene delivery to human breast tumor cells.
The influence of estradiol on the delivery of plasmid DNA to estrogen receptor positive MCF-7 human breast cancer cells was studied by the use of a reporter assay and by histochemical staining. Continuous exposure to estradiol enhanced the lipofectamine-mediated delivery of both pSV40-luciferase and pCMV beta-galactosidase in a concentration-dependent manner. Estradiol increased both the amount of pCMV beta-galactosidase per cell and the total fraction of cells competent to receive the transgene. The efficiency of transgene delivery to MCF-7 cells was further improved by repeating the transfection procedure in the presence of estradiol. Although overall gene uptake was reduced in control cells when studies were performed at room temperature (as opposed to 37 degrees C), potentiation of gene uptake by estradiol was maintained. At a concentration of 100 microM, estradiol also enhanced delivery of the transgene to estrogen receptor negative MDA-MB-231 breast tumor cells, indicating that the potentiating effects of estradiol are not mediated through the estrogen receptor. These studies are the first to raise the possibility that gene delivery to breast tumor cells can be improved by estradiol in single- or repeated-treatment regimens.
Department of Pharmacology, Medical College of Virginia, Virginia Commonwealth University, Richmond 23298, USA.
P T
PT
Jain
D A
DA
Gewirtz
D001943:Breast Neoplasms / Q000628:therapy*; D002411:Cation Exchange Resins; D003587:Cytomegalovirus / Q000235:genetics; D004958:Estradiol / Q000378:metabolism / Q000494:pharmacology*; D005260:Female; D018628:Gene Dosage; D015316:Genetic Therapy; D005822:Genetic Vectors; D006801:Humans; D008055:Lipids; D008081:Liposomes; D008156:Luciferases / Q000235:genetics; D013539:Simian virus 40 / Q000235:genetics; D013696:Temperature; D014162:Transfection; D014407:Tumor Cells, Cultured; D001616:beta-Galactosidase / Q000378:metabolism
D002411:Cation Exchange Resins; D008055:Lipids; C086724:Lipofectamine; D008081:Liposomes; D004958:Estradiol; D008156:Luciferases; D001616:beta-Galactosidase