Breast Cancer, Estrogen Receptor and Ligands

Abstract

This review emphasizes the relationship of breast cancer, estrogen receptor and ligands, especially the centrality of the estrogen receptor, which mediates on one hand the hormone-induced gene transcription and on the other hand the anti-estrogen action against breast cancer. The characterization of the estrogen receptor ligand-binding domain co-crystallized with agonists or antagonists provided a molecular basis to gain an insight into the regulation of estrogen receptor and, thereby, to describe the mechanism of the hormone therapy in treating breast cancer.

The role of estrogens and estrogen receptor signaling pathways in cancer and infertility: the case of schistosomes

“…The mechanism of target site specificity and selectivity seen with anti-estrogens, such as raloxifene, could be explained by the existence of two different ERs [29]. The receptor-specific regions are probably responsible for the differences seen between ERa and ERb, in spite of the high homology in the conserved regions of both ERs [20].…”

Novel roles of prolactin and estrogens in breast cancer: resistance to chemotherapy

“…The plethora of cell-specific co-activators and co-repressors account, in part, for the partial agonist versus antagonist activities of tamoxifen in the uterus, breast, bone, and cardiovascular system. Similar to the differential binding dynamics of the three lactogens to the PRLR (Gertler et al 1996), the various estrogenic ligands can induce distinct changes in ER conformation, thereby altering co-factor recruitment and receptor stability (Bai & Gust 2009). This is exemplified by an induction of rapid ERa degradation by the pure ER antagonist ICI 182 780, but not by E 2 or tamoxifen (Van Den Bemd et al 1999).…”

“…This indicates that most breast tumors express both receptors, reinforcing their importance as therapeutic targets. Finally is the issue of receptor promiscuity, with ERs capable of binding steroidal and nonsteroidal compounds (Bai & Gust 2009), and the PRLR capable of binding other lactogens . Thus, xenoestrogens can mimic or antagonize endogenous estrogens, while GH and placental lactogen (PL) can augment or interfere with PRL actions.…”

Emerging roles of Orai3 in pathophysiology

“…Numerous factors contribute to the development and progression of breast cancer such as genetic mutations, growth factors, and the presence or absence of estrogen receptors. [51][52][53][54] A large body of evidence suggests that Ca 2+ channels contribute to cancer progression. [55][56][57] When Orai channel isoforms are co-expressed with STIM1 in the HEK293 expression system, several groups have shown that these channels form store depletion-activated Ca 2+ channels.…”