Interaction of steroid hormone receptors with transcription factors involves chromatin remodelling

Beato, Miguel; Candau, Reyes; Chávez, Sebastián; Möws, Christian C.; Truss, Mathias

doi:10.1016/0960-0760(95)00223-5

Cited by 45 publications

(18 citation statements)

References 121 publications

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“…Steroid hormone receptors are known to interact with proteins directly involved in transcription as well as chromatin structure (Beato et al, 1996). Importantly, it was recently shown that there is a strict requirement for the HAT activity of p/CAF in transcriptional activation by nuclear receptors (Korzus et al, 1998).…”

Section: Discussionmentioning

confidence: 99%

“…Since ligand-bound ER is a major transcriptional activator of hPR B gene expression, the presence of PR in a cell is indicative of functional ER. Interestingly, it was recently shown that ER function is enhanced by its association with the coactivators SRC-1A, CREB binding protein (CPB) and p/CAF that all have intrinsic histone acetyltransferase (HAT) activity and play a role in remodeling the chromatin of estrogen responsive genes Smith et al, 1996;Korzus et al, 1998;Beato et al, 1996).…”

Section: Introductionmentioning

confidence: 99%

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Demethylation of the progesterone receptor CpG island is not required for progesterone receptor gene expression

1998

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Progesterone receptor (PR) is an estrogen-stimulated gene which has a CpG island that is heavily methylated in a signi®cant fraction of estrogen receptor (ER)-negative/PR-negative human breast cancers and cell lines, including MDA-MB-231 cells. Treatment of MDA-MB-231 cells with the demethylating agent, 5-aza-2'-deoxycytidine (deoxyC) led to demethylation and expression of ER and PR. However, simultaneous treatment with antiestrogen prevented PR transcription, suggesting that demethylation of PR alone is not su cient to reactivate the PR gene. To examine the e ects of ER on the methylation status of the PR CpG island, we stably transfected MDA-MB-231 cells with an inducible expression vector for ER. Surprisingly, in two cell clones, we found that induction of PR gene expression by ligand-bound ER does not require demethylation of the PR CpG island. In contrast, induction of PR transcription was inhibited by blocking the interaction of ER with SRC-1A, a coactivator of ER function. For the ®rst time, we show that a transcription factor with the potential to remodel heterochromatin can activate gene expression without altering the methylation status of the CpG island. These results raise the possibility that demethylation and histone acetylation are distinct but complementary mechanisms for destabilizing heterochromatin and activating transcription.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Demethylation of the progesterone receptor CpG island is not required for progesterone receptor gene expression

1998

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“…(Brzozowski et al, 1997 ;Picke et al, 2000). L'hélice 12 est essentielle à la fonction AF-2 (Danielian et al, 1992) et au recrutement des co-activateurs (Beato et al, 1996 ;Horwitz et al, 1996 ;Mc Kenna et al, 1999). En effet, la liaison de l'E2 permettrait l'interaction avec des co-activateurs du REα quand celle-ci serait impossible lors de la liaison d'antagonistes tels que le raloxifène (Brzozowski et al, 1997 ;Picke et al, 2000).…”

Section: Mécanismes Moléculaires D'action Des Resunclassified

The DHEA metabolite 7β-hydroxy-epiandrosterone exerts anti-estrogenic effects on breast cancer cell lines

et al. 2012

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Titre : La 7β-hydroxy-épiandrostérone dans des modèles in vitro de cancer du sein : effets anti-estrogéniques et rôle des récepteurs des estrogènes. La 7β-hydroxy-épiandrostérone, stéroïde endogène dérivant de la DHEA, présente des propriétés antiinflammatoires. En effet, elle module la voie des prostaglandines (PGs) en inhibant la production de la PGE2 pro-inflammatoires et en augmentant la production de la 15-Deoxy-∆ 12,14 -PGJ2 cyto-protectrice in vivo et in vitro. Les faibles doses de 7β-hydroxy-épiandrostérone (1nM, 10nM, 100nM) pour lesquelles ces effets sont observés, suggèrent une liaison à un récepteur spécifique. L'inflammation et la production des PGs jouent un rôle important dans le développement et la prolifération des tumeurs mammaires estrogéno-dépendantes. Le 17β-estradiol (E2), en se fixant sur les récepteurs des estrogènes (REs), induit la production de PGE2 et la prolifération cellulaire dans ces cellules tumorales. De ce fait, notre objectif était de tester les effets de la 7β-hydroxy-épiandrostérone sur la prolifération (comptage avec exclusion au bleu trypan), le cycle cellulaire et l'apoptose (cytométrie de flux) dans les lignées cellulaires de cancer du sein MCF-7 (REα+, REβ+, GPR30+) et MDA-MB-231 (REα-, REβ+, GPR30+) et d'identifier une(des) cible(s) potentielle(s) dans ces cellules (transactivation) et dans des cellules négatives pour les REs nucléaires SKBr3 (GPR30+) (études de prolifération). Cette étude a montré que la 7β-hydroxy-épiandrostérone exerce des effets anti-estrogéniques dans les cellules MCF-7 et MDA-MB-231 associés à une inhibition de la prolifération et un arrêt du cycle cellulaire. Les études de transactivation et de prolifération avec les agonistes spécifiques des REs ont montré une interaction avec le REβ. De plus, les résultats des études de proliférations sur les trois lignées cellulaires suggèrent que la 7β-hydroxy-épiandrostérone pourrait également interagir avec le GPR30. Ces résultats indiquent que ce stéroïde androgène agit comme un anti-estrogène. De plus, c'est la première fois qu'un stéroïde androgène à faible dose montre une action anti-proliférative dans des lignées de cancers du sein. De études ultérieures restent à réaliser afin de mieux comprendre ces effets observés. Mots clés : 7β-hydroxy-épiandrostérone, récepteurs des estrogènes, lignées de carcinomes mammaires, prolifération, transactivationThe DHEA metabolite 7β-hydroxy-epiandrosterone exerts anti-estrogenic effects on breast cancer cell lines 7β-hydroxy-epiandrosterone, an endogenous androgenic derivative of DHEA, has previously been shown to exert anti-inflammatory action in vitro and in vivo via a shift from prostaglandin E2 (PGE2) to 15-deoxy-∆ 12,14 -PGJ2 production. This modulation in prostaglandin production was obtained with low concentrations of 7β-hydroxy-epiandrosterone (1-100 nM) and suggested that it might act through a specific receptor. Inflammation and prostaglandin synthesis is important in the development and survival of estrogendependent mammary cancers. Estrogen induced PGE2 ...

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“…4 For instance, the steroid nuclear receptors can interact with hormone response elements in mouse mammary tumor virus (MMTV) promoter sequences. 5 In most cases, ligand binding to a nuclear receptor allows the recruitment of coactivator complexes possessing histone acetyltransferase activity, leading to chromatin decondensation and transcription initiation. 5,6 These properties have been exploited in the design of nuclear receptor reporter assays.…”

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confidence: 99%

“…5 In most cases, ligand binding to a nuclear receptor allows the recruitment of coactivator complexes possessing histone acetyltransferase activity, leading to chromatin decondensation and transcription initiation. 5,6 These properties have been exploited in the design of nuclear receptor reporter assays. By linking a response element with a reporter gene such as luciferase or alkaline phosphatase, the cellular activity of a nuclear receptor may be monitored in the presence or absence of its cognate ligand.…”

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confidence: 99%

Evaluation of Cell-Based Assays for Steroid Nuclear Receptors Delivered by Recombinant Baculoviruses

et al. 2005

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The authors describe the use of modified baculoviruses containing mammalian expression cassettes (BacMam technology) in steroid nuclear receptor reporter assays designed for screening and profiling agonist and antagonist compounds. Baculoviruses were constructed that express full-length human genes for mineralocorticoid receptor (MR), glucocorticoid receptor (GR), progesterone receptor A (PR-A), and progesterone receptor B (PR-B) from the cytomegalovirus immediate early promoter. A virus carrying the mouse mammary tumor virus-firefly luciferase (MMTV-Luc) cassette was generated to provide a suitable reporter construct. Feasibility studies with BacMam-MR in single-dose tests of 1000 compounds showed high correlation to the standard transfection-based assay results. Likewise, in dose-response experiments, BacMam-based assays for GR and PR-B produced potency and efficacy values similar to transfection assay results. At various receptor/reporter ratios, the BacMam assays showed good flexibility, demonstrating consistent signal-to-background (S/B) ratios and compound potencies. Increasing transduction time from 24 to 48 h provided no benefit, actually reducing overall assay performance as measured by S/B and Z′ values. The BacMam technology was applied in studies of isoforms PR-A and PR-B, which showed similar responses to a series of agonists. Taken together, the results demonstrate the utility of steroid nuclear receptor BacMam constructs for compound screening procedures with high reproducibility, reduced turnaround time, and lower cost. (Journal of Biomolecular Screening 2005:715-724)

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Interaction of steroid hormone receptors with transcription factors involves chromatin remodelling

Cited by 45 publications

References 121 publications

Demethylation of the progesterone receptor CpG island is not required for progesterone receptor gene expression

Demethylation of the progesterone receptor CpG island is not required for progesterone receptor gene expression

The DHEA metabolite 7β-hydroxy-epiandrosterone exerts anti-estrogenic effects on breast cancer cell lines

Evaluation of Cell-Based Assays for Steroid Nuclear Receptors Delivered by Recombinant Baculoviruses

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