Estrogen Receptor beta in Health and Disease1

Imamov, Otabek; Shim, Gil Jin; Warner, Margaret; Gustafsson, Jan‐Åke

doi:10.1095/biolreprod.105.043497

Cited by 93 publications

(68 citation statements)

References 94 publications

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“…The molecular basis of oestrogen action involves binding of the ligand to intracellular receptors which function as ligand-activated transcription factors (Oettel and Schillinger, 1999), but two oestrogen receptors (ERα and ERβ ) have now been characterized which vary in their tissue distributions and in their ligand binding af¼nities (Kuiper et al, 1997;Imamov et al, 2005). Whilst ERα levels are relatively higher in mammary and uterine tissue, and most notably in ER positive breast cancers, ERβ is more ubiquitously distributed and may mediate oestrogenic actions across non-reproductive tissues.…”

Section: Role Of Era and Erbmentioning

confidence: 99%

Paraben esters: review of recent studies of endocrine toxicity, absorption, esterase and human exposure, and discussion of potential human health risks

Darbre

Harvey

2008

J of Applied Toxicology

604

375

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This toxicology update reviews research over the past four years since publication in 2004 of the ¼rst measurement of intact esters of p-hydroxybenzoic acid (parabens) in human breast cancer tissues, and the suggestion that their presence in the human body might originate from topical application of bodycare cosmetics. The presence of intact paraben esters in human body tissues has now been con¼rmed by independent measurements in human urine, and the ability of parabens to penetrate human skin intact without breakdown by esterases and to be absorbed systemically has been demonstrated through studies not only in vitro but also in vivo using healthy human subjects. Using a wide variety of assay systems in vitro and in vivo, the oestrogen agonist properties of parabens together with their common metabolite ( p-hydroxybenzoic acid) have been extensively documented, and, in addition, the parabens have now also been shown to possess androgen antagonist activity, to act as inhibitors of sulfotransferase enzymes and to possess genotoxic activity. With the continued use of parabens in the majority of bodycare cosmetics, there is a need to carry out detailed evaluation of the potential for parabens, together with other oestrogenic and genotoxic co-formulants of bodycare cosmetics, to increase female breast cancer incidence, to interfere with male reproductive functions and to in½uence development of malignant melanoma which has also recently been shown to be in½uenced by oestrogenic stimulation.

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Section: Role Of Era and Erbmentioning

confidence: 99%

Paraben esters: review of recent studies of endocrine toxicity, absorption, esterase and human exposure, and discussion of potential human health risks

Darbre

Harvey

2008

J of Applied Toxicology

604

375

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“…It has been proposed that ERb could act as a dominant regulator of E2 signaling (Koehler et al 2005), and when co-expressed with ERa, it would cause a concentration-dependent reduction in ERamediated transcriptional activation (Pettersson et al 1997). The ERb-directed repression of ERa-mediated effects includes cell proliferation (Imamov et al 2005, Koehler et al 2005. Data from gene expression in cell cultures and knockout mice, clearly indicate that E2-activated ERb must have some function as a tumor suppressor by modulating the proliferative effects of ERa (Couse & Korach 1999, Cheng et al 2004, Paruthiyil et al 2004, Strom et al 2004.…”

Section: Introductionmentioning

confidence: 99%

Role of ERβ palmitoylation in the inhibition of human colon cancer cell proliferation

Galluzzo¹,

Caiazza²,

Moreno³

et al. 2007

Endocr Relat Cancer

100

113

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The cellular functions regulated by 17b-estradiol (E2) start after the hormone binds to its receptors (i.e., ERa and ERb). These act as ligand-dependent transcription factor transactivating target genes. In addition, E2 induces non-genomic actions, whose activation is triggered by a fraction of the ERs localized at the plasma membrane. Palmitoylation allows ERa to localize at the plasma membrane, to associate with caveolin-1, and, upon E2 stimulation, to activate rapid signals relevant for cell proliferation. The existence of a mechanism, which allows ERb localization at the plasma membrane and its putative role in anti-proliferative E2 effects is completely unknown. Here, the susceptibility of ERb to undergo palmitoylation and the role played by this process has been analyzed in DLD-1 containing endogenous ERb or in HeLa cells transiently transfected with ERb or ERa expression vectors. As for ERa, palmitoylation is necessary for ERb localization at the plasma membrane and its association with caveolin-1 but, in contrast to ERa, the E2 binding increases ERb association with caveolin-1 and the p38 member of MAPK family. Moreover, the palmitoyl acyl transferase (PAT) inhibitor blocks the ability of ERb-E2 complex to activate p38 impairing the receptor-dependent activation of downstream pro-apoptotic cascade (i.e., caspase-3 activation and poly(ADP-ribose)polymerase (PARP) cleavage). Consequently, palmitoylation must be considered to be a molecular device for ERb, which allows these receptors to interact with the plasma membrane and to regulate E2-induced non-genomic functions relevant to the antiproliferative effect of this hormone.

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“…The two ERs have highly homologous DNA-binding domains but significantly different N-terminus and ligand-binding domains. ERb is believed to regulate a set of physiological functions different from those regulated by ERa (Imamov et al, 2005).…”

Section: Introductionmentioning

confidence: 99%

AP-2 regulates the transcription of estrogen receptor (ER)-β by acting through a methylation hotspot of the 0N promoter in prostate cancer cells

Zhang

Leung

2007

Oncogene

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We reported previously that the loss of expression of estrogen receptor (ER)-b during the development of prostate cancer (PCa) is associated with methylation of a CpG island located in the 5 0 -flanking sequence of the 0N promoter. Three methylation hotspots, referred to as centers 1, 2 and 3, were identified in the CpG island. In this study, we demonstrated that a 581-bp region with these three centers within it is sufficient for the promoter activity in PCa cells. Deletion analyses indicated that center 1 (16 bp), with a putative activator protein-2 (AP-2) binding site, is essential for gene transactivation. Chromatin immunoprecipitation assays showed that AP-2a occupies a short sequence containing center 1. Forced expression of AP-2a or -2c, but not -2b, increased activity of the ERb 0N promoter and the accumulation of mRNA. Conversely, siRNA-mediated AP-2a and -2c knockdown reduced levels of ERb transcript and promoter activity. Quantitative reverse transcription-PCR showed that AP-2a and -2c are the predominant transcripts expressed in PCa cells, and levels of ERb transcript correlate with levels of these AP-2 transcripts among different PCa cell lines. These results provide the first evidence that ERb is an AP-2-regulated gene. They also support the hypothesis that certain cis-acting elements are methylation hotspots susceptible to epigenetic modifications during cancer progression.

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Estrogen Receptor beta in Health and Disease1

Cited by 93 publications

References 94 publications

Paraben esters: review of recent studies of endocrine toxicity, absorption, esterase and human exposure, and discussion of potential human health risks

Paraben esters: review of recent studies of endocrine toxicity, absorption, esterase and human exposure, and discussion of potential human health risks

Role of ERβ palmitoylation in the inhibition of human colon cancer cell proliferation

AP-2 regulates the transcription of estrogen receptor (ER)-β by acting through a methylation hotspot of the 0N promoter in prostate cancer cells

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