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.