The 5′ flanking region of the pS2 gene contains a complex enhancer region responsive to oestrogens, epidermal growth factor, a tumour promoter (TPA), the c-Ha-ras oncoprotein and the c-jun protein.

Rodríguez‐Núñez, Eugenio; Berry, Meera; Imler, Jean‐Luc; Chambon, Pierre

doi:10.1002/j.1460-2075.1989.tb03443.x

Cited by 250 publications

(120 citation statements)

References 68 publications

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“…To analyse whether treatment of breast cancer cells with PRL could also induce the recruitment of ERa and P-Ser-118-ERa to the target promoter, we performed chromatin immunoprecipitation (ChIP) assays in a-amanitin-synchronized populations of cells to compare pS2 promoter occupancy by the receptor in T47D cells incubated with PRL or E2. As shown in Figure 4, E2 recruited ERa to the pS2 promoter region containing the ERE and known to be required for E2 regulation of transcription (Nunez et al, 1989). This binding increased at 40 min and then decreased, in agreement with data obtained in other breast cancer cell line (MCF-7), where ERa recruitment to the promoter is cyclical (Shang et al, 2000;Metivier et al, 2003).…”

Section: Prl-dependent Activation Of Unliganded Ersupporting

confidence: 88%

“…To determine the effect of PRL on endogenous ERdependent gene expression, we analysed transcripts for the well-known estrogen target gene pS2, containing EREs in its regulatory region (Nunez et al, 1989). PRL significantly induced pS2 mRNA levels in T47D cells (Figure 2a), without increasing ERa mRNA levels (Figure 2b).…”

Section: Prl-dependent Activation Of Unliganded Ermentioning

confidence: 99%

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Activation of the unliganded estrogen receptor by prolactin in breast cancer cells

et al. 2009

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Both prolactin (PRL) and estrogen (E2) are involved in the pathogenesis and progression of mammary neoplasia, but the mechanisms by which these hormones interact to exert their effects in breast cancer cells are not well understood. We show here that PRL is able to activate the unliganded estrogen receptor (ER). In breast cancer cells, PRL activates a reporter plasmid containing estrogen response elements (EREs) and induces the ER target gene pS2. These actions are blocked by the antagonist ICI 182,780, showing that ER is required for the PRLmediated effect. Moreover, PRL leads to phosphorylation of ERa in serine-118 (P-ERa), a modification related to the potentiation of ligand-independent transcriptional activation. In addition, PRL mimics the effect of E2 on target gene expression by inducing cyclical recruitment of ERa and P-ERa to ERE-containing promoters, resulting in recruitment of co-activators and acetylation of histone H3. Finally, PRL induces expression of c-Myc and Cyclin D1 and leads to increased cell proliferation, which is specifically antagonized by ICI 182,780 or ERa depletion. These results show that ligand-independent ERa activation appears to be an important component of the proliferative and transcriptional actions of PRL in breast cancer cells.

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Section: Prl-dependent Activation Of Unliganded Ersupporting

confidence: 88%

Section: Prl-dependent Activation Of Unliganded Ermentioning

confidence: 99%

Activation of the unliganded estrogen receptor by prolactin in breast cancer cells

et al. 2009

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“…5), RhoGDIa differentially modulates the expression of the PR and pS2 genes, which have very different cis elements and trans-acting factors involved in conferring their hormone responsiveness. While the pS2 gene contains an imperfect ERE that interacts directly with ERa (Nunez et al 1989), the PR gene contains multiple AP-1 and Sp1 sites through which AP-1 and Sp1 proteins interact with ERa (Jeltsch et al 1987, Petz et al 2002, 2004a,b, Schultz et al 2003. Thus, we believe that the ability of RhoGDIa to differentially alter estrogen-responsive gene expression may be due to differences in the population of cis elements and the trans-acting factors associated with various target genes.…”

Section: Discussionmentioning

confidence: 99%

Rho GDP dissociation inhibitor α interacts with estrogen receptor α and influences estrogen responsiveness

Marzouk

Schultz-Norton

Likhite

et al. 2007

Journal of Molecular Endocrinology

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Estrogen receptor a (ERa) is a ligand-activated transcription factor that regulates expression of estrogen-responsive genes. Upon binding of the ligand-occupied ERa to estrogen response elements (EREs) in DNA, the receptor interacts with a variety of coregulatory proteins to modulate transcription of target genes. We have isolated and identified a number of proteins associated with the DNA-bound ERa. One of these proteins, Rho guanosine diphosphate (GDP) dissociation inhibitor a (RhoGDIa), is a negative regulator of the Rho family of GTP-binding proteins. In this study, we demonstrate that endogenously expressed RhoGDIa is present in the nucleus as well as the cytoplasm of MCF-7 breast cancer cells, and that RhoGDIa binds directly to ERa, alters the ERa-ERE interaction, and influences the ability of ERa to regulate transcription of a heterologous estrogen-responsive reporter plasmid in transient transfection assays as well as endogenous, estrogen-responsive genes in MCF-7 cells. Our studies suggest that, in addition to the activity of RhoGDIa in the cytoplasm, it also influences ERa signaling in the nucleus.

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“…Importantly, the human pS2 promoter contains binding sites for ERs as well as AP-1 transcription factors (78), indicating that expression of this gene, which had previously been demonstrated to be activated by cAMP in an ICI 164,384-inhibited manner, might involve cross-talk between ER and AP-1. Unexpectedly, pS2-CAT was not activated by ER␣ or ER␤ in response to forskolin/ IBMX treatment.…”

Section: Figmentioning

confidence: 96%

Mechanistic Differences in the Activation of Estrogen Receptor-α (ERα)- and ERβ-dependent Gene Expression by cAMP Signaling Pathway(s)

Coleman

Dutertre

El-Gharbawy

et al. 2003

Journal of Biological Chemistry

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Although increases in intracellular cAMP can stimulate estrogen receptor-␣ (ER␣) activity in the absence of exogenous hormone, no studies have addressed whether ER␤ can be similarly regulated. In transient transfections, forskolin plus 3-isobutyl-1-methylxanthine (IBMX), which increases intracellular cAMP, stimulated the transcriptional activities of both ER␣ and ER␤. This effect was blocked by the protein kinase A inhibitor H89 (N-(2-(p-bromocinnamylamino)-ethyl)-5-isoquinolinesulfonamide) and was dependent on an estrogen response element. A 12-O-tetradecanoylphorbol-13-acetate response element (TRE) located 5 to the estrogen response element was necessary for cAMP-dependent activation of gene expression by ER␤ but not ER␣, indicating that the former subtype requires a functional interaction with TRE-interacting factor(s) to stimulate transcription. Both p160 and CREB-binding protein coactivators stimulated cAMP-induced ER␣ and ER␤ transcriptional activity. However, mutation of the two cAMP-inducible SRC-1 phosphorylation sites important for cAMP activation of chicken progesterone receptor or all seven known SRC-1 phosphorylation sites did not specifically impair cAMP activation of ER␣. The E/F domains of ER␣ are sufficient for activation by forskolin/IBMX, and this is accompanied by an increase in receptor phosphorylation. In contrast, cAMP signaling reduces the phosphorylation of the corresponding region of ER␤, and this correlates with the lack of forskolin/IBMX stimulated transcriptional activity. Our data suggest that cAMP activation of ER␣ transcriptional activity is associated with receptor instead of SRC-1 phosphorylation. Moreover, differences in the cofactor requirements, domains of ER␣ and ER␤ sufficient for forskolin/IBMX activation, and the effect of cAMP on receptor phosphorylation indicate that this signaling pathway utilizes distinct mechanisms to stimulate ER␣ and ER␤ transcriptional activity.

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The 5′ flanking region of the pS2 gene contains a complex enhancer region responsive to oestrogens, epidermal growth factor, a tumour promoter (TPA), the c-Ha-ras oncoprotein and the c-jun protein.

Cited by 250 publications

References 68 publications

Activation of the unliganded estrogen receptor by prolactin in breast cancer cells

Activation of the unliganded estrogen receptor by prolactin in breast cancer cells

Rho GDP dissociation inhibitor α interacts with estrogen receptor α and influences estrogen responsiveness

Mechanistic Differences in the Activation of Estrogen Receptor-α (ERα)- and ERβ-dependent Gene Expression by cAMP Signaling Pathway(s)

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