Research Status Of Estrogen Receptor GPER In Breast Cancer

As we’v known, the response of cells to estrogen and its analogues, is mediated by ERa and ERβ which were regarded as classical nuclear receptor. In addition to mediate the genomic effect of cells, these receptors also mediates a series of "fast" cellular responses, that including the synthesis of cAMP and calcium mobilization. In addition to the classical estrogen nuclear receptor, It was identified a 7 transmembrane G protein coupled receptor GPER (called GPR30) by the research and literature records over the last 10 years/which has a certain function in the aspects of rapid effects of estrogen and cell gene expression. The cDNA of this receptor have multiple sources. Many research teams found that the activation of ERK1/2 and cAMP mediated by estrogen required GPER expression. In this later, various selective agonists and antagonists of GPER have been found.So far, the effect of GPER has been found is involving almost every physiological system, especially it plays an important role in hormone sensitive tumors. The classical estrogen receptor (ERa and ERβ) as well as estrogen is important factors effect on biological behavior of breast cancer, endometrial cancer and other various of hormone sensitive tumors. Endocrine therapy is an important part of comprehensive treatment to breast cancer, and selective estrogen receptor modulators (SERMs) for the estrogen antagonist in breast cancer has a history of several decades.But for the patients that have ER (-) breast cancer,especially the three negative breast cancer, it is particularly critical to find a new target for endocrine therapy to improve the prognosis of patients. The discovery of new estrogen receptor GPER, provides a new direction and ideas for us to further explore the mechanism and progress of breast cancer cells stimulated by estrogenand and endocrine targeted therapy to breast cancer.GPER is widely expressed in various tissues, but at present the intracellular localization of GPER is still no unified conclusion, generally speaking, most of the current view tend to consider that GPER was localized in the endocytoplasmic reticulum. The intracellular signal transduction pathway of GPER mainly include EGFR/MAPK,AC/cAMP /PKA, EGFR/STAT3, PI3K/AKT signaling pathway, which involved in cell proliferation, migration and angiogenesis process in breast cancer cells through the complex molecular mechanisms.Along with a large number of research we found that estrogen stimulation leads to the expression increase of GPER in TAM resistant cells, which in turn increases the sensitivity of cells to GPER agonists, which above proves that GPER and TAM resistant breast cancer has significant correlation. And it is found that in the MDA-MB-468 and MDA-MB-436 of TNBC cells in vitro, estrogen can activate GPER and its downstream EGFR/ERK signal pathway, which promote the expression of cyclin D1/A, Bcl-2, c-fos gene,involved in the regulation of TNBC’s cell proliferation, cell cycle and apoptosis, cell migration and invasion.In summary, the role of GPER in breast cancer is still controversial though, at least there are the results of the study show that, according to the GPER signal transduction pathway to create new drugs for molecular targeted therapy has become an effective strategy for the future research. Target recognition of two different types of estrogen receptor at the molecular level may further reduce the incidence and recurrence rate of breast cancer.