Subcelluar Localization Of Estrogen Receptor ERα And Its Relationship With Cell Proliferate

Estrogen receptor (ER), known as a hormone receptor, is one of the members of nucleus receptor (NR). ER has been shown to be activated in response to its ligand: steroid hormone 17?-estradiol (E2). As a mediator of estrogen action, the ER is involved in many important physiological processes, such as in spermary, ovary and neurocyte. At the same time, ER also participates in cell proliferation, differentiation and apoptosis.There are two kinds of ER, ERαand ERβ, which have four different functional regions. They are transcriptional activity domain, ligand binding domain, hinge domain and DNA binding domain. In this study, we constructed three different ERαmutants (ER△LBD,ER△DBD and ER△Hinge) to study the influence of ERαin cell proliferation and ERαsubcellular localization in response to E2. The results showed that in the 293T cell ERαlocalized more in the nucleus than in the cytoplasm. The ER△LBD localized in the cytoplasm, the ER△DBD was the same as ERα, and the ER△Hinge almost localized in the cytoplasm. We also found that the nuclear import of ERα, induced by E2, was nuclear location signal-dependent (NLS-dependent). Moreover, we showed that ERαcould increase proliferation of 293T cells and such increase depended on the ERαcapability of shuttling between the nucleus and the cytoplasm.Retinoic X receptors (RXRs) belongs to the steroid hormone receptor superfamily. RXRs have three different subspecies, RXRα,RXRβand RXRγ, which ligands are natural or synthetic vitamin A derivatives. RXRs play an important role in regulating a broad range of biological processes, including cell proliferation, differentiation and apoptosis.RXRαmay form heterodimer with ERα. However, its function in assistance of ERαtranslocation is still largely unknown. In our study, we indicated that RXRαhad an ability to assist ER△DBD and ER△Hinge translocation from the nucleus to the cytoplasm, and after treatment of E2, the ER△DBD returned to the nucleus while the ER△Hinge still localized in the cytoplasm. These results demonstrate that the different domains of ERαmay exert different functions when it interacts with RXRαin response to E2 treatment.To sum up, we demonstrate effects of different functional region of ERαin its subcellular localization and cellular proliferation. Our data reveal that RXRαcan assist the ER△DBD and ER△Hinge export from the nucleus. These findings will be helpful for further research on the functional mechanisms of ERαand E2 and prevention of breast cancer.