The subsequent demonstration that the pure antiestrogen ICI 164,384 could partially block EGF-induced, uterine DNA synthesis indicated that at least a portion of the proliferative response was mediated by the ER and suggested that EGF signaling pathways could cross-talk with the ER.
Growth factors also mimic estrogens in their ability to increase the expression of ER target genes, such as the progesterone receptor (PR) and the iron-binding glycoprotein, lactoferrin. Early experiments demonstrated that treatment of MCF-7 breast cancer or primary uterine cells with IGF-I or EGF increased PR binding activity. Cotreatment with either of the ER antagonists LY 117,018 or ICI 164,384 blocked growth factor as well as estradiol induction of PR expression, suggesting that both stimuli could activate ER function. In animals treated with EGF, lactoferrin expression is elevated in uterine epithelial cells. This increased expression of this gene is similar to that observed in mice treated with the synthetic estrogen diethylstilbestrol. levitra super active plus
More recently, experiments done with the ERa knockout (ERKO) mouse also support the hypothesis that some of the cellular effects of EGF are mediated via the ER. Both alleles of the ERa gene have been disrupted by homologous recombination in the ERKO mouse, and a preliminary report indicates that ER(3 expression patterns do not appear to be significantly altered in these animals. Expression of ER(3 is not detectable in mouse uterus, and estrogenic responses in this organ are presumably the result of ERa activity. EGF treatment of ERKO mice does not increase uterine DNA synthesis as it does in wild type animals, nor can it induce PR mRNA expression.