The inability of EGF to elicit these proliferative and transcriptional effects in the ERKO mouse is not due to a general defect in EGF signaling. Wild-type and ERKO mice express comparable levels of EGF-receptor in the uterus, which autophosphorylates in response to EGF challenge. Furthermore, induction of the EGF target gene, c-fos, is robust in wild-type and knock-out mouse uterine tissue. Taken together, these data indicate that EGF exerts some of its biological responses in an ER-dependent manner and, therefore, provides evidence that growth factor signaling pathway(s) can cross-talk with, and regulate, the activity of the ER in vivo. Buy Asthma Inhalers Online
The ability of ER antagonists to block some of the cellular actions of growth factors suggested that this nuclear receptor may be capable of receiving direct inputs from signal transduction pathways. Several experiments suggest that EGF stimulation can alter some of the ER’s biochemical properties. It is well established that estrogen treatment increases the proportion of ER in the nucleus in comparison to the cytoplasm and enhances the receptor’s affinity for chromatin. In cells treated with EGF, most ER is found in the nuclear compartment. In addition, this nuclear ER appears as heterogenous bands by Western blot analysis, just as receptor obtained from estrogen-treated cells also yields multiple bands. Alterations in ER mobility assessed by this method are associated with increased receptor phosphorylation, which suggests that the ER may be a direct target of growth factor signaling pathways.