Estrogen Receptor ß in Cancer: To ß(e) or not to ß(e)?

Abstract

Estrogen receptors (ERs) are known to play an important role in the proper development of estrogen-sensitive organs, as well as in the development and progression of various types of cancer. ERα, the first ER to be discovered, has been the focus of most cancer research, especially in the context of breast cancer. However, ERβ expression also plays a significant role in cancer pathophysiology, notably its seemingly protective nature and loss of expression with oncogenesis and progression. While ERβ exhibits anti-tumor activity in breast, ovarian, and prostate cancer, its expression is associated with disease progression and worse prognosis in lung cancer. The function of ERβ is complicated by the presence of multiple isoforms and single nucleotide polymorphisms, in addition to tissue-specific functions. This mini-review explores current literature on ERβ and its mechanism of action and clinical implications in breast, ovarian, prostate, and lung cancer.

Overview of BPH: Symptom Relief with Dietary Polyphenols, Vitamins and Phytochemicals by Nutraceutical Supplements with Implications to the Prostate Microbiome

“…Equol has a chiral center at carbon 3, and thus, can exist in two mirror image forms or enantiomers (S-equol and R-equol), which (1) are both biologically active and can specifically bind free 5α-DHT, an important aspect for BPH treatment [ 13 , 107 , 109 ], (2) can be found in plants, food, and animal products [ 13 , 110 ], (3) are classified as phytoestrogens that act like selective estrogen receptor modulators (SERMS) that bind ERβ receptors in the prostate to protect against BPH [ 13 , 110 , 111 , 112 , 113 ], (4) provide an inhibitory action on the aromatase enzyme that is responsible for estrogen biosynthesis and cellular proliferation [ 114 , 115 ] and, (5) can be biosynthesized to high purity for commercial use in human topical and oral applications [ 116 ]. Comparisons of the chemical structures of 17β-Estradiol and Equol are shown in Figure 6 .…”

“…Equol’s mechanisms of action: (1) directly by binding free serum 5α-DHT [ 13 , 119 ], (2) as a 5α-reductase enzyme inhibitor [ 119 ], (3) as a moderate aromatase enzyme inhibitor [ 114 , 115 ], (4) by inhibiting NFkβ and stimulating nuclear factor-erythroid factor 2-related factor 2 (Nrf2) expression to decrease inflammation and enhance antioxidant/detoxification enzyme expression, respectively, (5) as a SERM to protect the prostate by binding ERβ [ 13 , 113 ], (6) by binding estrogen-related-receptor-gamma (ERR-γ) that appears to play an important role in prostate health [ 13 , 118 ], and (7) for approximately 6 to 8 h (T ½ half-life) after taken orally [ 109 ] without side effects; then equol may provide beneficial efficacy to treat BPH symptoms that are not present in current pharmaceutical treatments (see Figure 8 ).…”

The role of sex hormones and receptors in HBV infection and development of HBV‐related HCC

“…ERα is primarily responsible for mediating estrogen-activated signaling pathways, while the specific biological processes mediated by ERβ are still under investigation. 52 ERα consists of three domains: the N-terminal domain (NTD), DNA binding domain (DBD), and ligand-binding domain (LBD). The NTD and LBD contain activation function domains (AF), which regulate the transcriptional activity of ERα.…”

“…Estrogen exerts its effects through two distinct receptors, ERα and ERβ. ERα is primarily responsible for mediating estrogen‐activated signaling pathways, while the specific biological processes mediated by ERβ are still under investigation 52 . ERα consists of three domains: the N‐terminal domain (NTD), DNA binding domain (DBD), and ligand‐binding domain (LBD).…”

Estrogens, Cancer and Immunity

“…In breast cancers, however, it is lost. ERβ agonists in ERα-positive cancers have antiproliferative properties [23]. New data prove that ERβ inhibits breast cancer cell migration and invasion via Claudin-6 (CLDN6)-mediated autophagy.…”