Human Estrogen Receptor β-Gene Structure, Chromosomal Localization, and Expression Pattern1

Enmark, Eva; Pelto‐Huikko, Markku; Grandien, Kaj; Lagercrantz, Svetlana; Lagercrantz, Jacob; Fried, Gabriel; Nordenskjöld, Magnus; Gustafsson, Jan Åke

doi:10.1210/jcem.82.12.4470

Cited by 350 publications

(78 citation statements)

References 25 publications

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“…Synthetic compounds also regulate gene expression in prostate cancer cells through ER␤, which is the predominant ER subtype in those cells (18)(19)(20). Being dependent on agonistic ligands such as E2, ER directly binds to estrogen response elements (EREs) within genomic DNA to induce gene expression (classical pathway) (21).…”

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confidence: 99%

Estrogen Exhibits a Biphasic Effect on Prostate Tumor Growth through the Estrogen Receptor β-KLF5 Pathway

Nakajima

Osakabe

Waku

et al. 2016

Molecular and Cellular Biology

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h Estrogens are effective in the treatment of prostate cancer; however, the effects of estrogens on prostate cancer are enigmatic. In this study, we demonstrated that estrogen (17␤-estradiol [E2]) has biphasic effects on prostate tumor growth. A lower dose of E2 increased tumor growth in mouse xenograft models using DU145 and PC-3 human prostate cancer cells, whereas a higher dose significantly decreased tumor growth. We found that anchorage-independent apoptosis in these cells was inhibited by E2 treatment. Similarly, in vivo angiogenesis was suppressed by E2. Interestingly, these effects of E2 were abolished by knockdown of either estrogen receptor ␤ (ER␤) or Krüppel-like zinc finger transcription factor 5 (KLF5). ⌱n addition, E2 suppressed KLF5-mediated transcription through ER␤, which inhibits proapoptotic FOXO1 and proangiogenic PDGFA expression. Furthermore, we revealed that a nonagonistic ER ligand GS-1405 inhibited FOXO1 and PDGFA expression through the ER␤-KLF5 pathway and regulated prostate tumor growth without ER␤ transactivation. Therefore, these results suggest that E2 biphasically modulates prostate tumor formation by regulating KLF5-dependent transcription through ER␤ and provide a new strategy for designing ER modulators, which will be able to regulate prostate cancer progression with minimal adverse effects due to ER transactivation.

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confidence: 99%

Estrogen Exhibits a Biphasic Effect on Prostate Tumor Growth through the Estrogen Receptor β-KLF5 Pathway

Nakajima

Osakabe

Waku

et al. 2016

Molecular and Cellular Biology

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“…Many published studies since the discovery of ERβ in 1997 indicated that ERβ was distributed in the human tissues and more expressed in the normal colonic epithelium, suggesting that estrogens may play an important role in the growth of normal colonic mucosa [31,32]. In addition to the above estrogen β receptor considered the dominant receptor type in normal colonic tissue and its down-regulation may be linked to the progression of colorectal cancer [33].…”

Section: Discussionmentioning

confidence: 99%

Value of estrogen receptor β expression in normal colon mucosa and colorectalcancer: an immunohistochemical analysis

Hassan¹,

Hegazy²,

Mosaed³

2015

J Histol Histopathol

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Estrogens (ER) have a protective role against colorectal carcinoma (CRC). Reduction of death from CRC has been observed in women (30%) as compared to men (7%) in particular with the users of oral contraception and in those women treated with Hormone Replacement Therapy (HRT). The aim of this study is to analyze the expression of estrogen receptor β (ERβ) in normal colonic mucosa and in CRC. The archival material of formalin-fixed-paraffin embedded tissue sections of 10 cases of normal colonic mucosa and 25specimens of CRCwere utilized in this study. An immunohistochemistry using avidin-biotin immuno-enzymatic technique (ABT) for the expression of ERβ primary mouse monoclonal antibody was performed. ER is expressed in 3 out of 10 cases of normal colonic mucosa. CRC revealed different levels of ERβ expression regardless of patient age, gender, grade, invasion, or lymph node status. ERβpositive immunostaining is more common in well differentiated tumors and in lower stage of disease than in poor differentiated one and advanced stage of CRC. The immunopositivity of ERβ in CRC is seen in 56% of cases, whereas its negativity is 44%.

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“…Two years later ERβ was definitively identified as a 530 residue protein [138]. ERα and ERβ are the products of two genes belonging to different chromosomes (6q25.1 and 14q23-24.1 respectively) [139, 140]. Although only two ERs have been found in mammals, a third ER (ERγ) has been identified in fish species [141].…”

Section: Molecular Mechanismsmentioning

confidence: 99%

Combating Malaria with Plant Molecules: A Brief Update

Negi¹,

Gupta²,

Hamid

2013

CMC

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Observations on the role of ovarian hormones in breast cancer growth, as well as interest in contraception, stimulated research into the biology of estrogens. The identification of the classical receptors ERα and ERβ and the transmembrane receptor GPER and the resolution of the structure of the ligand bound to its receptor established the principal molecular mechanisms of estrogen action. The presence of estrogen-like compounds in many plants used in traditional medicine or ingested as food ingredients, phytoestrogens, as well as the estrogenic activities of many industrial pollutants and pesticides, xenoestrogens, have prompted investigations into their role in human health. Phyto- and xenoestrogens bind to the estrogen receptors with a lower affinity than the endogenous estrogens and can compete or substitute the hormone. Xenoestrogens, which accumulate in the body throughout life, are believed to increase breast cancer risk, especially in cases of prenatal and prepuberal exposure whereas the role of phytoestrogens is still a matter of debate. At present, the application of phytoestrogens appears to be limited to the treatment of post-menopausal symptoms in women where the production of endogenous estrogens has ceased. In this review we discuss chemistry, structure and classification, estrogen signaling and the consequences of the interactions of estrogens, phytoestrogens and xenoestrogens with their receptors, the complex interactions of endogenous and exogenous ligands, the evaluation of the health risks related to xenoestrogens, and the perspectives toward the synthesis of potent third generation selective estrogen receptor modulators (SERMs).

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Human Estrogen Receptor β-Gene Structure, Chromosomal Localization, and Expression Pattern1

Cited by 350 publications

References 25 publications

Estrogen Exhibits a Biphasic Effect on Prostate Tumor Growth through the Estrogen Receptor β-KLF5 Pathway

Estrogen Exhibits a Biphasic Effect on Prostate Tumor Growth through the Estrogen Receptor β-KLF5 Pathway

Value of estrogen receptor β expression in normal colon mucosa and colorectalcancer: an immunohistochemical analysis

Combating Malaria with Plant Molecules: A Brief Update

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