Possible role of phytoestrogens in breast cancer via GPER-1/GPR30 signaling.

Estrogens generated within endocrine organs and the reproductive system act as ligands for at least three types of estrogen receptors. Estrogen receptors α (ERα) and β (ERβ) belong to the so-called classical family of estrogen receptors, whereas the G protein-coupled receptor GPR30, also known as GPER-1, has been described as a novel estrogen receptor sited in the cell membrane of target cells. Furthermore, these receptors are under stimulation of a family of exogenous estrogens, known as phytoestrogens, which are a diverse group of non-steroidal plant compounds derived from plant food consumed by humans and animals. Because phytoestrogens are omnipresent in our daily diet, they are becoming increasingly important in both human health and disease. Recent evidence indicates that in addition to classical estrogen receptors, phytoestrogens also activate GPER-1 a relevant observation since GPER-1 is involved in several physiopathological disorders and especially in estrogen-dependent diseases such as breast cancer.The first estrogen receptors discovered were the classical ERα and ERβ, but from an evolutionary point of view G protein-coupled receptors trace their origins in history to over a billion years ago suggesting that estrogen receptors like GPER-1 may have been the targets of choice for ancient phytoestrogens and/or estrogens.This review provides a comprehensive and systematic literature search on phytoestrogens and its relationship with classical estrogen receptors and GPER-1 including its role in breast cancer, an issue still under discussion.

Molina L ，Bustamante FA ，Bhoola KD ，Figueroa CD ，Ehrenfeld P ... -  《-》

GPER-1/GPR30 a novel estrogen receptor sited in the cell membrane: therapeutic coupling to breast cancer.

Molina L ，Figueroa CD ，Bhoola KD ，Ehrenfeld P ... -  《-》

Baicalein has protective effects on the 17β-estradiol-induced transformation of breast epithelial cells.

Chen Y ，Wang J ，Hong DY ，Chen L ，Zhang YY ，Xu YN ，Pan D ，Fu LY ，Tao L ，Luo H ，Shen XC ... -  《Oncotarget》

GPER Mediates Non-Genomic Effects of Estrogen.

Pupo M ，Maggiolini M ，Musti AM 《-》

The G protein-coupled estrogen receptor as a modulator of neoplastic transformation.

Estrogens play a crucial role in the regulation of physiological and pathophysiological processes. These hormones act through specific receptors, most notably the canonical estrogen receptors α and β (ERα and ERβ) and their truncated forms as well as the G protein-coupled estrogen receptor (GPER). Several studies have shown that GPER is expressed in many normal and cancer cells, including those of the breast, endometrium, ovary, testis and lung. Hormonal imbalance is one possible cause of cancer development. An accumulating body of evidence indicates that GPER is involved in the regulation of cancer cell proliferation, migration and invasion, it may act as a mediator of microRNA, and is believed to modulate the inflammation associated with neoplastic transformation. Furthermore, used in various treatment regimens anti-estrogens such as tamoxifen, raloxifen and fulvestrant (ICI 182.780), antagonists/modulators of canonical estrogen receptors, were found to be GPER agonists. This review presents the current knowledge about the potential role of GPER in neoplastic transformation.

Jacenik D ，Cygankiewicz AI ，Krajewska WM 《-》