Functional characteristics of a novel murine estrogen receptor-beta isoform, estrogen receptor-beta 2

Lü, Biao; Leygue, Etienne; Dotzlaw, Helmut; Murphy, LJ; Murphy, LJ

doi:10.1677/jme.0.0250229

Cited by 32 publications

(37 citation statements)

References 47 publications

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“…31,32 Interestingly, in breast, 25 ovary 25-28 and endometrium, 29 malignancy is associated with loss of ERb expression while in adenocarcinoma of the esophagus 30 increased expression is seen. One study has shown decreased ERb expression in colonic adenocarcinoma 31 while another study 32 suggests that, as [33][34][35] as well as evidence that the interaction of ERa and ERb levels may play a role in carcinogenesis. 28 The demonstration of ERb in vascular neoplasms suggests a role for estrogen antagonists in the therapy of the most aggressive vascular tumors: angiosarcomas.…”

Section: Discussionmentioning

confidence: 99%

Estrogen receptor β expression in vascular neoplasia: an analysis of 53 benign and malignant cases

et al. 2004

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The importance of estrogen in vascular neoplasia is suggested by a predilection for women and a tendency for rapid growth during pregnancy. Although early experiments using radioligand assays demonstrated estrogen receptor (ER) expression, these findings were not confirmed by subsequent immunohistochemical studies which were performed with antibodies raised against ERa. A newly discovered estrogen receptor subtype, ERb, has not been previously characterized in vascular lesions. In order to verify the expression of estrogen receptors in vascular neoplasms as well as to clarify the inconsistency between radioligand and early immunohistochemical studies, we examined a series of 53 benign and malignant vascular neoplasms for ERb expression. All of the subtypes of vascular neoplasia examined had nuclear expression of ERb. The majority of cases (94%) displayed 2 þ to 3 þ staining. The discrepancy between radioligand studies and previous immunohistochemical studies is attributable to the use of antibodies raised against ERa, which is not expressed in vascular lesions, and not ERb, which is broadly expressed in both benign and malignant vascular neoplasms. Although ERb may be of limited diagnostic use in vascular neoplasia due to its broad expression, the potential exists for a therapeutic approach using ER agonists. The role of estrogen in vascular neoplasia has long been suspected due to the observation that vascular neoplasms tend to grow rapidly during pregnancy and in adolescence. 1 These clinical observations were initially substantiated by early experiments in the 1980s using radioligand assays, which confirmed the presence of the estrogen receptor (ER) in vascular tumors; 2,3 however, with the advent of immunohistochemical techniques, subsequent studies performed in the 1990s with antibodies raised against the ER refuted these earlier data and it appeared that the newer technology had exposed the limitations of the older biochemical assays. [4][5][6][7] Recently, an additional ER subtype, estrogen receptor beta (ERb), 8 was identified and the previous ER against which the original antibodies were raised was renamed estrogen receptor alpha (ERa). Although ERa has been assessed immunohistochemically in vascular neoplasms and found to be absent, ERb has not been previously characterized in these entities. In order to verify the expression of ER in vascular tumors as well as to clarify the inconsistency between radioligand and early immunohistochemical studies, we examined a series of 53 benign and malignant vascular neoplasms for ERb expression. Materials and methodsIn all, 22 cases of angiosarcoma, three cases of Kaposi sarcoma, one case of epithelioid hemangioendothelioma, two cases of spindle-cell hemangioma, four cases of infantile hemangioendothelioma, 13 cases of hemangioma, seven cases of lymphangioma and one case of papillary endothelial hyperplasia were identified and retrieved from the paraffin archives of the University of Chicago. Formalin-fixed paraffin-embedded specimens were cut into 4-mm sections an...

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Section: Discussionmentioning

confidence: 99%

Estrogen receptor β expression in vascular neoplasia: an analysis of 53 benign and malignant cases

et al. 2004

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“…4B and C ;Nardulli & Shapiro 1993, Lu et al 2000. The calculated bending angle for hER was 64·8 1 (mean S.E.M, n=3), for hER 1 it was 53·6 0·5 and for hER 2 it was 54·6 0·7.…”

Section: Dna Binding and Bending Activity Of Her 1 And Variant Isoformentioning

confidence: 94%

“…Ligand binding studies were conducted as previously described (Lu et al 2000). In vitro-generated receptor was diluted 10-fold in buffer (10 mM Tris-HCl, pH 7·5, 1·5 mM EDTA, 10 mg/ml BSA, 10% glycerol) and kept on ice until use.…”

Section: Scatchard Analysismentioning

confidence: 99%

“…This promoter was shown to be preferentially activated by the raloxifene-bound hER compared with estradiol in cultured cells (Yang et al 1996), and we have previously shown differential abilities of murine ER isoforms to affect this promoter compared with EREcontaining promoters (Lu et al 2000). Therefore, the activity of hER isoforms on TGF -3-CAT was examined (Fig.…”

Section: Transcriptional Activity Of Her 1 Her 2 and Hermentioning

confidence: 99%

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Putative functional characteristics of human estrogen receptor-beta isoforms

Peng¹,

Lü²,

Leygue³

et al. 2003

Journal of Molecular Endocrinology

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112

107

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Estrogen receptors (ERα and ERβ) are clearly multifaceted in terms of structure and function. Several relatively abundant ERβ isoforms have been identified, which can be differentially expressed in various tissues. In order to provide insight into the possible role of the ERβ family in breast tissue a study of the putative functions of the human (h) ERβ1, hERβ2 and hERβ5 isoforms was undertaken. Only hERβ1 was found to bind ligand, which induced conformational changes as determined by protease digestion assays. All ERβ isoforms could bind to and bend DNA although the relative efficiency with which they bound DNA differed with hERα>hERβ1>hERβ2> >hERβ5. All ERβ isoforms inhibited ERα transcriptional activity on an estrogen-response element (ERE)-reporter gene. The relative activities were hERβ1>hERβ2 >hERβ5; however, only hERβ1 had transcriptional activity of its own. Both LY117018-hERα and LY117018-hERβ1 complexes alone could activate transcription on a TGF-β3-CAT gene. Although hERβ2 and hERβ5 had no activity alone, they inhibited ERα but not hERβ1 transcriptional activity of transforming growth factor (TGF)-β3-CAT. In marked contrast to activity on an ERE-CAT reporter gene, hERβ1 did not modulate ERα transcriptional activity on a TGF-β3-CAT reporter gene. These data support promoter-specific differential activities of hERβ isoforms with respect to models of ERα regulated gene expression, and suggest that they may have a role in differentially modulating estrogen action.

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“…The DNA-binding domain is intact and electrophoretic mobility shift assays have shown binding ability of ERb ins to estrogen responsive element (ERE). [19][20][21] It has been proposed that this receptor isoform might act as a dominant negative regulator of estrogen signaling. 19,22 Interestingly, the affinity of ERb ins for the antiestrogen, Tamoxifen, is similar to that of ERb1.…”

Section: Introductionmentioning

confidence: 99%

Spatiotemporal dynamics of the expression of estrogen receptors in the postnatal mouse brain

Sugiyama

Andersson

Lathe³

et al. 2008

Mol Psychiatry

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This study reports on the spatiotemporal dynamics of the expression of estrogen receptors (ERs) in the mouse central nervous system (CNS) during the early postnatal and the peripubertal period. At postnatal day 7 (P7), neurons with strong nuclear immunostaining for both ERa and ERb1 were widely distributed throughout the brain. Sucrose density gradient sedimentation followed by western blotting supported the histochemical evidence for high levels of both ERs at P7. Over the following 2 days, there was a rapid downregulation of ERs. At P9, ERa expression was visible only in the hypothalamic area. Decline in ERb1 expression was slower than that of ERa, and ERa-negative, ERb1-positive cells were observed in the dentate gyrus and walls of third ventricle. Between P14 and P35, ERs were undetectable except for the hypothalamic area. As before P7, the ovary does not produce estrogen but does produce 5a-androstane-3b, 17b-diol (3bAdiol), an estrogenic metabolite of dihydrotestosterone, we examined the effects of high levels of 3bAdiol in the postnatal period. We used CYP7B1 knockout mice which cannot hydroxylate and inactivate 3bAdiol. The brains of these mice are abnormally large with reduced apoptosis. In the early postnatal period, there was 1-week delay in the timing of the reduction in ER expression in the brain. These data reveal that the time when ERs might be activated in the brain is limited to the first 8 postnatal days. In addition, the importance of aromatase has to be reconsidered as the alternative estrogen, 3bAdiol, is important in neuronal function in the postnatal brain.

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Functional characteristics of a novel murine estrogen receptor-beta isoform, estrogen receptor-beta 2

Abstract: We have isolated a highly expressed splice variant mRNA of murine estrogen receptor-(ER

Cited by 32 publications

References 47 publications

Estrogen receptor β expression in vascular neoplasia: an analysis of 53 benign and malignant cases

Estrogen receptor β expression in vascular neoplasia: an analysis of 53 benign and malignant cases

Putative functional characteristics of human estrogen receptor-beta isoforms

Spatiotemporal dynamics of the expression of estrogen receptors in the postnatal mouse brain

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