Structure–function relationship of estrogen receptor α and β: Impact on human health

Ascenzi, Paolo; Bocedi, Alessio; Marino, Maria

doi:10.1016/j.mam.2006.07.001

Cited by 456 publications

(550 citation statements)

References 629 publications

(927 reference statements)

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“…However, ERa and ERb are also localized at the plasma membrane where they initiate 17b-estradiol (E2)-induced rapid signals (22). Evidence accumulated suggests that ERa-dependent rapid membrane-starting actions are crucial for the E2-induced cancer promoting response in several target cells (22). Therefore, it is reasonable to suggest that BPA, similarly to E2, binds to ERa and produces changes in these rapid signals.…”

Section: Introductionmentioning

confidence: 99%

Expression of Concern: Laccase treatment impairs bisphenol A‐induced cancer cell proliferation affecting estrogen receptor α‐dependent rapid signals

et al. 2008

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SummaryA wide variety of environmental contaminants exert estrogenic actions in wildlife, laboratory animals, and in human beings through binding to nuclear estrogen receptors (ERs). Here, the mechanism(s) of bisphenol A (BPA) to induce cell proliferation and the occurrence of its bioremediation by treatment with laccase are reported. BPA, highly present in natural world and considered as a model of environmental estrogen action complexity, promotes human cancer cell proliferation via ERa-dependent signal transduction pathways. Similar to 17b-estradiol, BPA increases the phosphorylation of both extracellular regulated kinase and AKT. Specific inhibitors of these kinase completely block the BPA effect on cancer cell proliferation. Notably, high BPA concentrations (i.e., 0.1 and 1 mM) are cytotoxic even in ERa-devoid cancer cells, indicating that an ERa-independent mechanism participates to BPA-induced cytotoxicity. On the other hand, BPA oxidation by laccase impairs the binding of this environmental estrogen to ERa loosing at all ERa-dependent effect on cancer cell proliferation. Moreover, the laccase-catalyzed oxidation of BPA reduces the BPA cytotoxic effect. Thus, laccase appears to impair BPA action(s), representing an invaluable bioremediation enzyme.2008 IUBMB IUBMB Life, 60(12): 843-852, 2008

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Section: Introductionmentioning

confidence: 99%

Expression of Concern: Laccase treatment impairs bisphenol A‐induced cancer cell proliferation affecting estrogen receptor α‐dependent rapid signals

et al. 2008

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“…ERα and ERβ are encoded by separate genes found at different chromosomal locations. While sharing a high homology in both DNA binding domain and ligand binding domain, ERα and ERβ have very low sequence identity in both N-(12%) and C-terminals (9%), correspond to AF1 and AF2 domain, respectively (Ascenzi et al, 2006). Hence, it is not surprising that ERβ has very low classic transcriptional activity, when compared with ERα (Lubahn et al, 1993;Cowley et al, 1997;Pettersson et al, 1997;Ogawa et al, 1998;Cowley and Parker, 1999;Curtis et al, 2000;Yi et al, 2002).…”

Section: Mitochondrial Localization Of Erβmentioning

confidence: 99%

Estrogen actions on mitochondria—Physiological and pathological implications

Simpkins

Yang

Sarkar

et al. 2008

Molecular and Cellular Endocrinology

135

105

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Estrogens are potent neuroprotective hormones and mitochondria are the site of cellular life-death decisions. As such, it is not surprising that we and other have shown that estrogens have remarkable effects on mitochondrial function. Herein we provide evidence for a primary effect of estrogens on mitochondrial function, achieved in part by the import of estrogen receptor β (ERβ) into the mitochondria where it mediates a number of estrogen actions on this vital organelle. ERβ is imported into the mitochondria, through tethering to cytosolic chaperone protein and/or through direct interaction with mitochondrial import proteins. In the mitochondria, ERβ can affect transcription of critical mitochondrial genes through the interaction with estrogen response elements (ERE) or through protein-protein interactions with mitochondrially imported transcription factors. The potent effects of estrogens on mitochondrial function, particularly during mitochondrial stress, argues for a role of estrogens in the treatment of mitochondrial defects in chronic neurodegenerative diseases like Alzheimer's disease (AD) and Parkinson's disease (PD) and more acute conditions of mitochondrial compromise, like cerebral ischemia and traumatic brain injury.

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“…1A) for binding to ERs and modify their activity as ligand-dependent transcriptional regulators (Hall et al . 2001, Ascenzi et al . 2006).…”

Section: Introductionmentioning

confidence: 99%

Antiestrogens: structure-activity relationships and use in breast cancer treatment

Traboulsi

Ezzy

Gleason

et al. 2017

Journal of Molecular Endocrinology

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About 70% of breast tumors express estrogen receptor alpha (ERα), which mediates the proliferative effects of estrogens on breast epithelial cells, and are candidates for treatment with antiestrogens, steroidal or non-steroidal molecules designed to compete with estrogens and antagonize ERs. The variable patterns of activity of antiestrogens (AEs) in estrogen target tissues and the lack of systematic cross-resistance between different types of molecules have provided evidence for different mechanisms of action. AEs are typically classified as selective estrogen receptor modulators (SERMs), which display tissue-specific partial agonist activity (e.g. tamoxifen and raloxifene), or as pure AEs (e.g. fulvestrant), which enhance ERα post-translational modification by ubiquitin-like molecules and accelerate its proteasomal degradation. Characterization of second- and third-generation AEs, however, suggests the induction of diverse ERα structural conformations, resulting in variable degrees of receptor downregulation and different patterns of systemic properties in animal models and in the clinic.

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Structure–function relationship of estrogen receptor α and β: Impact on human health

Cited by 456 publications

References 629 publications

Expression of Concern: Laccase treatment impairs bisphenol A‐induced cancer cell proliferation affecting estrogen receptor α‐dependent rapid signals

Expression of Concern: Laccase treatment impairs bisphenol A‐induced cancer cell proliferation affecting estrogen receptor α‐dependent rapid signals

Estrogen actions on mitochondria—Physiological and pathological implications

Antiestrogens: structure-activity relationships and use in breast cancer treatment

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