EGF activates highly selective estrogen-responsive reporter plasmids by an ER-independent pathway.
Epidermal growth factor (EGF) mimics the effects of estrogen on some cells, suggesting that it may activate the estrogen receptor (ER). We examined the ability of EGF to increase expression of several different estrogen-responsive luciferase reporters in MCF-7 breast cancer cells. Although EGF increased reporter activity, this effect was not inhibited by estrogen antagonists and was not dependent on estrogen response elements in the reporter plasmid. Similar results were obtained in BG-1 (ovarian) and Ishikawa (uterine) cells. In ER-negative JEG-3 cells, EGF, but not estradiol, increased reporter activity in the absence of transfected ER. The estrogen antagonist ICI 182780 blocked the ability of estradiol, but not EGF, to stimulate proliferation of T47D breast cancer cells, suggesting that the mitogenic effects of EGF are not mediated by ER. EGF does not appear to activate ER-mediated transcription in these experimental systems, although crosstalk between the estrogen and EGF signaling pathways may occur by other mechanisms.
Gehm
B D
BD
Division of Endocrinology, Metabolism and Molecular Medicine, Northwestern University Medical School, Chicago, IL 60611, USA.
McAndrews
J M
JM
Jordan
V C
VC
Jameson
J L
JL
D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D004958:Estradiol / Q000031:analogs & derivatives / Q000494:pharmacology*; D020847:Estrogen Receptor Modulators / Q000494:pharmacology; D005260:Female; D000077267:Fulvestrant; D017930:Genes, Reporter / Q000187:drug effects*; D006801:Humans; D008156:Luciferases / Q000235:genetics; D010957:Plasmids / Q000235:genetics; D017434:Protein Structure, Tertiary; D011960:Receptors, Estrogen / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D014162:Transfection; D014407:Tumor Cells, Cultured
D020847:Estrogen Receptor Modulators; D011960:Receptors, Estrogen; D000077267:Fulvestrant; D004958:Estradiol; D004815:Epidermal Growth Factor; D008156:Luciferases