Aryl hydrocarbon receptor-independent activation of estrogen receptor-dependent transcription by 3-methycholanthrene

Shipley, Jonathan; Waxman, David J.

doi:10.1016/j.taap.2005.09.011

Cited by 51 publications

(39 citation statements)

References 32 publications

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“…In other studies, AhR ligands have been found to activate ER-mediated transcriptional activity without a requirement for the AhR (Abdelrahim et al, 2006;Shipley and Waxman, 2006). Abdelrahim et al (2006) reported that AhR ligands 3-methylcholanthrene and 3,3Ј,4,4Ј,5-pentachlorobiphenyl were capable of activating ERs in MCF7 breast cancer cells, whereas Shipley and Waxman (2006) found that 3-methylcholanthrene but not 3,3Ј,4,4Ј,5-pentachlorobiphenyl or TCDD functioned as an ER agonist in Ishikawa uterine cancer cells. In another study, Boverhof et al (2006) reported that TCDD treatment of ovariectomized mice altered the expression of numerous uterine genes that were comparably regulated by 17␣-ethynylestradiol.…”

Section: Downloaded Frommentioning

confidence: 97%

“…Concerning proestrogenic effects, Ohtake et al (2003) reported that AhR ligand treatment can induce ER-mediated transcription through the formation of an AhR ⅐ ARNT ⅐ ER complex (Brosens and Parker, 2003). In other studies, AhR ligands have been found to activate ER-mediated transcriptional activity without a requirement for the AhR (Abdelrahim et al, 2006;Shipley and Waxman, 2006). Abdelrahim et al (2006) reported that AhR ligands 3-methylcholanthrene and 3,3Ј,4,4Ј,5-pentachlorobiphenyl were capable of activating ERs in MCF7 breast cancer cells, whereas Shipley and Waxman (2006) found that 3-methylcholanthrene but not 3,3Ј,4,4Ј,5-pentachlorobiphenyl or TCDD functioned as an ER agonist in Ishikawa uterine cancer cells.…”

Section: Downloaded Frommentioning

confidence: 99%

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Regulation of Estrogen Sulfotransferase Expression by Confluence of MCF10A Breast Epithelial Cells: Role of the Aryl Hydrocarbon Receptor

Fu¹,

Fang²,

Paulsen³

et al. 2011

J Pharmacol Exp Ther

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Estrogen sulfotransferase (SULT1E1) catalyzes the sulfonation of estrogens, which limits estrogen mitogenicity. We recently reported that SULT1E1 expression is low in preconfluent MCF10A human breast epithelial cells but increases when the cells become confluent. Pulse-chase labeling experiments with 5-bromouridine demonstrated that the confluence-mediated increase in SULT1E1 expression was due to increased mRNA synthesis. Because aryl hydrocarbon receptor (AhR) activation has been shown to suppress SULT1E1 expression and loss of cell-cell contact has been shown to activate the AhR in other cell types, we tested whether the confluence-associated changes in SULT1E1 expression were mediated by the AhR. Relative to confluent MCF10A cells, preconfluent cells had higher levels of CYP1A1 mRNA and greater activation of an AhR-responsive luciferase reporter, demonstrating that the AhR was active in the preconfluent cells. AhR and aryl hydrocarbon receptor nuclear translocator mRNA and protein levels were also higher in preconfluent than in confluent cultures. Treatment of preconfluent cells with the AhR antagonist, 3Ј-methoxy-4Ј-nitroflavone (MNF), or AhR knockdown significantly increased SULT1E1 expression. MCF10A cells stably transfected with a luciferase reporter containing ϳ7 kilobases of the SULT1E1 5Ј-flanking region showed both MNF-and confluence-inducible luciferase expression. Preconfluent cells transiently transfected with the reporter showed both MNF treatment-and AhR knockdown-mediated luciferase induction, but mutation of a computationally predicted dioxin response element (DRE) at nucleotide (nt) Ϫ3476 did not attenuate these effects. These results demonstrate that SULT1E1 expression in MCF10A cells is transcriptionally regulated by confluence through a suppressive action of the AhR, which is not mediated through a DRE at nt Ϫ3476.

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Section: Downloaded Frommentioning

confidence: 97%

Section: Downloaded Frommentioning

confidence: 99%

Regulation of Estrogen Sulfotransferase Expression by Confluence of MCF10A Breast Epithelial Cells: Role of the Aryl Hydrocarbon Receptor

Fu¹,

Fang²,

Paulsen³

et al. 2011

J Pharmacol Exp Ther

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“…TransIT-LT1 was preincubated with serum free medium for 5 min and added to the Hoechst dye-DNA mix and further incubated for 15 min. The mix was then added equally to each well to be transfected (Shipley and Waxman, 2006). Transfections were performed using the following amounts of plasmid DNA per well of a 48-well tissue culture plate: 10 ng of receptor plasmid (AR, ERα, ERβ, TRβ, PR-B, RARα, RARβ or RARγ), 90 ng of reporter plasmid (pPB-luc, ERC3-luciferase, pTK-TR(DR4) 3 , progesterone receptor reporter plasmid or pGL3-β-RARE-luc), 20 ng of pSV-βgal (for normalization of luciferase activity) and 130 ng salmon sperm DNA.…”

Section: Plasmidsmentioning

confidence: 99%

Interactions of methoxyacetic acid with androgen receptor

Bagchi

Hurst

Waxman

2009

Toxicology and Applied Pharmacology

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Endocrine disruptive compounds (EDC) alter hormone-stimulated, nuclear receptor-dependent physiological and developmental processes by a variety of mechanisms. One recently identified mode of endocrine disruption is through hormone sensitization, where the EDC modulates intracellular signaling pathways that control nuclear receptor function, thereby regulating receptor transcriptional activity indirectly. Methoxyacetic acid (MAA), the primary, active metabolite of the industrial solvent ethylene glycol monomethyl ether and a testicular toxicant, belongs to this EDC class. Modulation of nuclear receptor activity by MAA could contribute to the testicular toxicity associated with MAA exposure. In the present study, we evaluated the impact of MAA on the transcriptional activity of several nuclear receptors including the androgen receptor (AR), which plays a pivotal role in the development and maturation of spermatocytes. AR transcriptional activity is shown to be increased by MAA through a tyrosine kinase signaling pathway that involves PI3-kinase. In a combinatorial setting with AR antagonists, MAA potentiated the AR response without significantly altering the EC 50 for androgen responsiveness, partially alleviating the antagonistic effect of the antiandrogens. Finally, MAA treatment of TM3 mouse testicular Leydig cells markedly increased the expression of Cyp17a1 and Shbg while suppressing Igfbp3 expression by ∼90%. De-regulation of these genes may alter androgen synthesis and action in a manner that contributes to MAA-induced testicular toxicity.

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“…DIM has been reported not only to inhibit estrogenic responses (26) but also to activate ERα in the absence of 17β-estradiol (E 2 ) via protein kinase A-mediated phosphorylation (27,28). Although AHR agonists such as 3-methylcholanthrene have been reported to enhance ER-dependent responses (29,30), two independent studies have shown that the estrogenic activity of 3-methylcholanthrene is independent of AHR (31,32). Moreover, a number of AHR ligands have been shown to directly activate ERα, defining a new class of bifunctional AHR/ERα agonists (33,34).…”

Section: Introductionmentioning

confidence: 99%

Estrogen Receptor Subtype– and Promoter-Specific Modulation of Aryl Hydrocarbon Receptor–Dependent Transcription

Wihlén

Ahmed

Inzunza

et al. 2009

Molecular Cancer Research

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In this study, we examined the role of estrogen receptors (ER) in aryl hydrocarbon receptor (AHR)-dependent transactivation. Chromatin immunoprecipitation assays showed that AHR agonists differentially induced recruitment of ERα to the AHR target genes CYP1A1 and CYP1B1. Cotreatment with 17β-estradiol significantly increased β-naphthoflavone (BNF)-and 2,3,7,8-tetrachlorodibenzop-dioxin-induced recruitment of ERα to CYP1A1, whereas 3,3′-diindolylmethane induced promoter occupancy of ERα at CYP1A1 that was unaffected by cotreatment with 17β-estradiol. Cyclical recruitment of AHR and ERα to CYP1A1 was only observed in cells treated with BNF. Stable and subtype-specific knockdown of ERα or ERβ using shRNA showed that suppression of ERα significantly reduced, whereas knockdown of ERβ significantly enhanced, AHR agonist-induced Cyp1a1 expression in HC11 mouse mammary epithelial cells. AHR agonist-induced Cyp1b1 expression was reduced by ERβ knockdown but unaffected by ERα knockdown. The siRNA-mediated knockdown of ERα in MCF-7 human breast cancer cells did not affect 2,3,7,8-tetrachlorodibenzo-p-dioxin-dependent regulation of CYP1A1 and CYP1B1 mRNA expression. In agreement with our in vitro findings in the HC11 cells, ERα knockout mice exhibit reduced BNF-dependent induction of Cyp1a1 mRNA. These results establish ligand-and promoter-specific influences on the cyclical recruitment patterns for AHR and show ER species-, subtype-, and promoter-specific modulation of AHR-dependent transcription. (Mol Cancer Res 2009;7(6):977-86)

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Aryl hydrocarbon receptor-independent activation of estrogen receptor-dependent transcription by 3-methycholanthrene

Cited by 51 publications

References 32 publications

Regulation of Estrogen Sulfotransferase Expression by Confluence of MCF10A Breast Epithelial Cells: Role of the Aryl Hydrocarbon Receptor

Regulation of Estrogen Sulfotransferase Expression by Confluence of MCF10A Breast Epithelial Cells: Role of the Aryl Hydrocarbon Receptor

Interactions of methoxyacetic acid with androgen receptor

Estrogen Receptor Subtype– and Promoter-Specific Modulation of Aryl Hydrocarbon Receptor–Dependent Transcription

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