Estrogen Receptor β-Selective Transcriptional Activity and Recruitment of Coregulators by Phytoestrogens

An, Jinping; Tzagarakis-Foster, Christina; Scharschmidt, Tiffany C.; Lomri, Noureddine; Leitman, Dale C.

doi:10.1074/jbc.m100953200

Cited by 299 publications

(181 citation statements)

References 63 publications

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“…Antibody directed to ER-b did not react with proteins at the expected size of 58 ± 62 kDa in homogenate, nuclear or plasma membrane fractions of MCF-7 cells (see Fuqua et al, 1999). This is consistent with several reports that ®nd little to no ER-b transcripts in MCF-7 cells (Register and Adams, 1998;An et al, 2001). Finally, a minor band at 97-kDa was detected in plasma membrane and other cell fractions by use of immunoblotting with antibodies to ER-a and with ligand-blotting.…”

Section: Discussionsupporting

confidence: 78%

Membrane-associated binding sites for estrogen contribute to growth regulation of human breast cancer cells

2001

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Membrane-associated binding sites for estrogen may mediate rapid eects of estradiol-17b that contribute to proliferation of human breast cancers. After controlled homogenization and fractionation of MCF-7 breast cancer cells, the bulk of speci®c estradiol binding is found in nuclear fractions. However, a signi®cant portion of speci®c, high-anity estradiol-17b binding-sites are also enriched in plasma membranes. These estradiol binding-sites co-purify with 5'-nucleotidase, a plasma membrane-marker enzyme, and are free from major contamination by cytosol or nuclei. Electrophoresis of membrane fractions allowed detection of a primary 67-kDa protein and a secondary 46-kDa protein recognized by estradiol-17b and by a monoclonal antibody directed to the ligand-binding domain of the nuclear form of estrogen receptor. Estrogen-induced growth of MCF-7 breast cancer cells in vitro was blocked by treatment with the antibody to estrogen receptor and correlated closely with acute hormonal activation of mitogenactivated protein kinase and Akt kinase signaling. Estrogen-promoted growth of human breast cancer xenografts in nude mice was also signi®cantly reduced by treatment in vivo with the estrogen receptor antibody. Thus, membrane-associated forms of estrogen receptor may play a role in promoting intracellular signaling for hormone-mediated proliferation and survival of breast cancers and oer a new target for antitumor therapy. Oncogene (2001) 20, 5420 ± 5430.

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Section: Discussionsupporting

confidence: 78%

Membrane-associated binding sites for estrogen contribute to growth regulation of human breast cancer cells

2001

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“…In addition, phytoestrogens have been shown to induce transactivation via both ER subtypes (27), with an increased transcriptional response through ER . They are, however, less potent than E 2 via both ER subtypes (27,28).…”

Section: Introductionmentioning

confidence: 99%

Evaluation of the Phytoestrogenic Activity of Cyclopia genistoides (Honeybush) Methanol Extracts and Relevant Polyphenols

Verhoog

Joubert

Louw

2007

J. Agric. Food Chem.

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Unfermented C. genistoides methanol extracts of different harvestings and selected polyphenols were evaluated for phytoestrogenic activity by comparing binding to both ER subtypes, transactivation of an ERE-containing promoter reporter, proliferation of MCF-7-BUS and MDA-MB-231 breast cancer cells, and binding to SHBG. The extracts from one harvesting of C. genistoides (P104) bound to both ER subtypes. All extracts transactivated ERE-containing promoter reporters via ER but not via ERR. All extracts, except P122, caused proliferation of the estrogen-sensitive MCF-7-BUS cells. Proliferation of MCF-7-BUS cells was ER-dependent as ICI 182,780 reversed proliferation. Physiologically more relevant, extracts antagonized E 2 -induced MCF-7-BUS cell proliferation. Furthermore, all extracts, except P122, induced proliferation of the estrogen-insensitive MDA-MB-231 cells, suggesting that the extracts are able to induce ER-dependent and ER-independent cell proliferation. Binding to SHBG by extracts was also demonstrated. These results clearly show that C. genistoides methanol extracts display phytoestrogenic activity and act predominantly via ER . HPLC and LC-MS analysis, however, suggests that the observed phytoestrogenic activity cannot be ascribed to polyphenols known to be present in other Cyclopia species.

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“…As isoflavonas podem agir como SERMs naturais ou fito-SERMs, visto que podem modular o receptor de estrogênio 8 . Esse fato ajudaria a compreender sua ação no alívio dos sintomas climatéricos, sobretudo nos fogachos, sem causar efeitos proliferativos no endométrio e na mama.…”

Section: Introductionunclassified

Efeitos das isoflavonas sobre o miométrio de ratas adultas

Mosquette¹,

Gomes²,

Simões³

et al. 2006

Rev. Bras. Ginecol. Obstet.

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RESUMOObjetivo: avaliar as alterações no miométrio de ratas após o tratamento com isoflavonas, comparando-as às dos estrogênios, por técnicas histológicas e morfométricas. Métodos: 28 ratas adultas castradas foram divididas, ao acaso, em quatro grupos que receberam: GPropi -propilenoglicol; GExtr10 -extrato de soja (10 mg/kg por dia); GExtr300 -extrato de soja (300 mg/kg por dia) e GEce -estrogênios conjugados eqüinos (Ece -200 µg/kg por dia). Após 21 dias de tratamento, todos os animais foram sacrificados, os úteros retirados e pesados, e fragmentos dos cornos uterinos foram coletados e fixados em formol a 10% e processados para inclusão em parafina. Os cortes histológicos foram corados pela hematoxilina e eosina e examinados em microscópio acoplado a analisador de imagens para avaliação da espessura, número de vasos sanguíneos e de eosinófilos no miométrio. Os resultados obtidos foram submetidos à análise de variância (ANOVA), seguida pelo teste de comparações múltiplas de Tukey-Kramer. Resultados: as isoflavonas, na concentração de 300 mg/kg, induziram aumento significante na espessura do miométrio (GExtr300=25,6±5,0 mm) em relação ao controle (GPropi=5,5±0,5 mm). O efeito desta alta é comparável ao efeito dos estrogênios (GEce=27,5±7,9 mm). Em doses baixas (10 mg/kg), os valores foram similares ao controle. Além disso, as isoflavonas (GExtr300) induziram aumento no número de vasos sangüíneos (GExtr300=10,2±3,6/mm 2 ; GPropi=3,5±1,6 vasos/mm 2 ) e de eosinófilos (GExtr300=4,3±0,9; GPropi=0,15±0,01 eosinófilos/mm 2 ), igualmente comparáveis aos efeitos obtidos pelo tratamento com Ece (GEce=9,2±1,1 eosinophils/mm 2 ). Conclusão: as isoflavonas em doses altas (300 mg/kg por dia, durante 21 dias) têm efeito proliferativo no miométrio de ratas, semelhante ao dos estrogênios. PALAVRAS-CHAVE:Isoflavonas; Estrogênios; Miométrio; Estudo experimental ABSTRACT Purpose: to evaluate histomorphometric changes in the rat myometrium upon treatment with isoflavones, as compared with estrogens, using histological and morphometric techniques. Methods: twenty-eight oophorectomized adult rats were randomly divided into four treatment groups: GPropi = propylene glycol (control); GExtr10 -10 mg/kg soybean extract; GExtr300 -300 mg/kg soy bean extract; GCee -200 µg/kg conjugated equine estrogens (Cee). Drugs or drug vehicle were administered by gavage once a day for 21 days. Upon sacrifice, the uteri were removed and weighed. Fragments of uterine horns were collected and fixed in 10% formaldehyde and processed for paraffin inclusion. The histological sections were stained by hematoxylin and eosin and evaluated microscopically by means of an image analyzer to quantify the myometrial thickness and the number of blood vessels and eosinophils. The data were studied by analysis of variance (ANOVA) followed by the Tukey-Kramer multiple comparison test. Results: isoflavones in the concentration of 300 mg/kg induced a significant increase in the myometrium thickness (GExtr300=25.6±5.0 mm) compared to control (GPropi=5.5±0.5 mm). The effect ...

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Estrogen Receptor β-Selective Transcriptional Activity and Recruitment of Coregulators by Phytoestrogens

Cited by 299 publications

References 63 publications

Membrane-associated binding sites for estrogen contribute to growth regulation of human breast cancer cells

Membrane-associated binding sites for estrogen contribute to growth regulation of human breast cancer cells

Evaluation of the Phytoestrogenic Activity of Cyclopia genistoides (Honeybush) Methanol Extracts and Relevant Polyphenols

Efeitos das isoflavonas sobre o miométrio de ratas adultas

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