Mechanisms Of Aryl Hydrocarbon Receptor And Estrogen Receptor Action In Breast Cancer Cells

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Mechanisms of Aryl Hydrocarbon Receptor and Estrogen Receptor Action in Breast Cancer Cells

Author : Jeong Eun Lee
Publisher :
ISBN 13 :
Total Pages : pages
Book Rating : 4.:/5 (796 download)

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Book Synopsis Mechanisms of Aryl Hydrocarbon Receptor and Estrogen Receptor Action in Breast Cancer Cells by : Jeong Eun Lee

Download or read book Mechanisms of Aryl Hydrocarbon Receptor and Estrogen Receptor Action in Breast Cancer Cells written by Jeong Eun Lee and published by . This book was released on 2006 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: In MCF7 and T47D cells cotreated with 1 nM 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) plus 0.1-10 uM 3̕,4̕ -dimethoxy flavone (DMF), there was a concentration-dependent decrease in the TCDD-induced ethoxyresorufin O-deethylase (EROD) activity. Gel mobility shift assays showed that 3̕,4̕ -DMF inhibited TCDD-induced aryl hydrocarbon receptor (AhR) transformation in rat liver cytosol and blocked TCDD-induced formation of the nuclear AhR complex in MCF7 and T47D cells. The antiestrogenic activity of TCDD in estrogen-induced transactivation assays in MCF7 cells was reversed by 3̕,4̕ -DMF, confirming the AhR antagonist activity of this compound in breast cancer cells. Cotreatment of T47D and MCF7 cells with TCDD and 10 uM resveratrol inhibited induction of CYP1A1 mRNA and EROD activity. Resveratrol did not inhibit TCDD-induced AhR transformation and reporter gene activity. Actinomycin D chase experiments in T47D cells showed that the mechanism of inhibition of CYP1A1 mRNA and EROD activity is due to an increased rate of CYP1A1 mRNA degradation, suggesting that resveratrol inhibits CYP1A1 via an AhR-independent post-transcriptional pathway. Vitamin D receptor-interacting protein 150 (DRIP150) coactivated estrogen receptor [alpha] (ER [alpha])-mediated transactivation and the response was AF2-dependent in ZR75 breast cancer cells. C-and N-terminal NR-boxes (amino acids 1186-1182 and 73-69, respectively) were not necessary for coactivation of ER [alpha]. Analysis of DRIP150 deletion mutants identified a 23 amino acid sequence (811-789) required for coactivation. The 23 amino acid contained two regions at amino acids 789-794 and 795-804 which resembled [alpha] -helical motifs identified in Lanuguinosa lipase/histamine N-methyl transferase and hepatocyte nuclear factor 1, respectively. A squelching assay using specific point mutations within each [alpha] -helix showed that the NIFSEVRVYN (795-804) region was the critical sequence required for the coactivator activity of DRIP150.

Activation of Estrogen Receptor Alpha, Aryl Hydrocarbon Receptor, and Nuclear Factor Erythroid-2 Like 2 in Human Breast Cancer Cells

Author : Raymond Ho Fai Lo
Publisher :
ISBN 13 :
Total Pages : pages
Book Rating : 4.:/5 (13 download)

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Book Synopsis Activation of Estrogen Receptor Alpha, Aryl Hydrocarbon Receptor, and Nuclear Factor Erythroid-2 Like 2 in Human Breast Cancer Cells by : Raymond Ho Fai Lo

Download or read book Activation of Estrogen Receptor Alpha, Aryl Hydrocarbon Receptor, and Nuclear Factor Erythroid-2 Like 2 in Human Breast Cancer Cells written by Raymond Ho Fai Lo and published by . This book was released on 2013 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt:

Discovery and Mechanism of Action of Anti-cancer Compounds Targeting the Aryl Hydrocarbon Receptor

Author : Edmond F. O'Donnell
Publisher :
ISBN 13 :
Total Pages : 428 pages
Book Rating : 4.:/5 (845 download)

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Book Synopsis Discovery and Mechanism of Action of Anti-cancer Compounds Targeting the Aryl Hydrocarbon Receptor by : Edmond F. O'Donnell

Download or read book Discovery and Mechanism of Action of Anti-cancer Compounds Targeting the Aryl Hydrocarbon Receptor written by Edmond F. O'Donnell and published by . This book was released on 2013 with total page 428 pages. Available in PDF, EPUB and Kindle. Book excerpt: The aryl hydrocarbon receptor (AhR) is a ligand activated transcription factor belonging the basic helix-loop-helix Per/Arnt/Sim (bHLH PAS) family of proteins. The AhR has long been studied for its role in mediating the effects of environmental toxicants, most notably 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). By studying the mechanism of action of TCDD, the AhR has been shown to be involved in numerous biological functions and processes, including metabolism of xenobiotics, the adaptive immune response, embryonic development, and cell cycle regulation. The AhR has also been shown to act as a tumor suppressor gene in several mouse models of cancer. In addition, the AhR is highly expressed in a number of different cancers. We hypothesized that structurally diverse ligands of the AhR have different effects on AhR function, and that it is possible to activate anti-cancer properties of the AhR without inducing dioxin-like toxicity. To this end, we screened a small molecule library of pharmacologically active compounds including FDA-approved drugs, with the specific intent of repurposing such drugs as AhR-based anti- cancer therapeutics. We used a parallel screening approach, with one assay utilizing a xenobiotic response element (XRE) based reporter assay to identify traditional ligands of the AhR, and a second system consisting of a novel heterologous AhR-dependent reporter assay designed to identify novel AhR ligands distinct from those that activate XRE-driven genes. Using these approaches, and evaluating the phenotypic effects of putative hits in target cancer cell types, four lead compounds were selected for further evaluation, two of which are currently in use in clinic: leflunomide, used to treatment rheumatoid arthritis, and raloxifene, a selective estrogen receptor (ER) modulator used to prevent osteoporosis and ER-positive breast cancer. The mechanisms of action of the lead compounds were characterized in terms of AhR activation and AhR- dependent anti-cancer effects. We showed that leflunomide inhibits growth of melanoma cells in an AhR-dependent manner through a mechanism distinct from its current use in the clinic. Two of the lead compounds were found to induce AhR-dependent apoptosis, with raloxifene exhibiting anti-cancer effects in hormone-independent breast cancer cells. The AhR ligands characterized in this work, including leflunomide and raloxifene, represent a novel small molecule probe set that can be used to better characterize the anti-cancer properties of the AhR. The AhR-dependent phenotypes of these compounds compared to AhR ligands such as TCDD will also be useful for establishing a molecular basis for how the AhR facilitates diverse biological outcomes in response to activation by distinct ligands. Development of these compounds, especially raloxifene, as AhR-targeted anti- cancer therapeutics will be useful for establishing the AhR as a viable anti-cancer target.

Molecular Mechanisms of Aryl Hydrocarbon Receptor Transactivation and Crosstalk with Estrogen Receptor Alpha

Author : Shaimaa Ahmed
Publisher :
ISBN 13 : 9780494930779
Total Pages : pages
Book Rating : 4.9/5 (37 download)

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Book Synopsis Molecular Mechanisms of Aryl Hydrocarbon Receptor Transactivation and Crosstalk with Estrogen Receptor Alpha by : Shaimaa Ahmed

Download or read book Molecular Mechanisms of Aryl Hydrocarbon Receptor Transactivation and Crosstalk with Estrogen Receptor Alpha written by Shaimaa Ahmed and published by . This book was released on 2012 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt:

Modulation of Aryl Hydrocarbon and Estrogen Receptor Mediated-responses by Nuclear Receptor Coregulators in Breast Cancer Cells

Author : Thu Anh Nguyen
Publisher :
ISBN 13 :
Total Pages : 484 pages
Book Rating : 4.:/5 (498 download)

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Book Synopsis Modulation of Aryl Hydrocarbon and Estrogen Receptor Mediated-responses by Nuclear Receptor Coregulators in Breast Cancer Cells by : Thu Anh Nguyen

Download or read book Modulation of Aryl Hydrocarbon and Estrogen Receptor Mediated-responses by Nuclear Receptor Coregulators in Breast Cancer Cells written by Thu Anh Nguyen and published by . This book was released on 2001 with total page 484 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Hormonally Active Agents in the Environment

Author : National Research Council
Publisher : National Academies Press
ISBN 13 : 0309064198
Total Pages : 453 pages
Book Rating : 4.3/5 (9 download)

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Book Synopsis Hormonally Active Agents in the Environment by : National Research Council

Download or read book Hormonally Active Agents in the Environment written by National Research Council and published by National Academies Press. This book was released on 2000-02-03 with total page 453 pages. Available in PDF, EPUB and Kindle. Book excerpt: Some investigators have hypothesized that estrogens and other hormonally active agents found in the environment might be involved in breast cancer increases and sperm count declines in humans as well as deformities and reproductive problems seen in wildlife. This book looks in detail at the science behind the ominous prospect of "estrogen mimics" threatening health and well-being, from the level of ecosystems and populations to individual people and animals. The committee identifies research needs and offers specific recommendations to decision-makers. This authoritative volume: Critically evaluates the literature on hormonally active agents in the environment and identifies known and suspected toxicologic mechanisms and effects of fish, wildlife, and humans. Examines whether and how exposure to hormonally active agents occursâ€"in diet, in pharmaceuticals, from industrial releases into the environmentâ€"and why the debate centers on estrogens. Identifies significant uncertainties, limitations of knowledge, and weaknesses in the scientific literature. The book presents a wealth of information and investigates a wide range of examples across the spectrum of life that might be related to these agents.

Arl-Hydrocarbon Receptor Based Antiestrogenicity of Diindolylmethane Analogs

Author :
Publisher :
ISBN 13 :
Total Pages : 0 pages
Book Rating : 4.:/5 (946 download)

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Book Synopsis Arl-Hydrocarbon Receptor Based Antiestrogenicity of Diindolylmethane Analogs by :

Download or read book Arl-Hydrocarbon Receptor Based Antiestrogenicity of Diindolylmethane Analogs written by and published by . This book was released on 2002 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: Research in our laboratory has been focused on the mechanism of inhibitory aryl hydrocarbon (Ah) receptor-estrogen receptor a (ER alpha) crosstalk in breast cancer cells, and results indicate that Ah receptor agonists inhibit estrogen (E2)-induced gene expression and cell proliferation (1,2). Moreover, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), a high affinity ligand for the Ah receptor, inhibits age-dependent and carcinogen-induced mammary tumor formation and growth in female Sprague-Dawley rats, and a recent study reported that women accidentally exposed to TCDD in Seveso, Italy, over 20 years ago exhibit lower incidence rates of breast and endometrial cancer (3). Studies on various structural classes of AhR agonists have identified alternate substituted (1,3,6,8- or 2,4,6,8- ) alkyl polychlorinated dibenzofurans (PCDFs) and substituted diindolylmethanes (DlMs) as selective Ah receptor modulators (SAhRMs) that are relative nontoxic but inhibit mammary tumor growth in rodent models (4). With financial support from this grant, I have been investigating the indirect antiestrogenic activity of substituted DIMs and applications of these compounds for treating mammary cancer (5-7).

Biomarkers in Breast Cancer

Author : Giampietro Gasparini
Publisher : Springer Science & Business Media
ISBN 13 : 159259915X
Total Pages : 335 pages
Book Rating : 4.5/5 (925 download)

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Book Synopsis Biomarkers in Breast Cancer by : Giampietro Gasparini

Download or read book Biomarkers in Breast Cancer written by Giampietro Gasparini and published by Springer Science & Business Media. This book was released on 2008-01-17 with total page 335 pages. Available in PDF, EPUB and Kindle. Book excerpt: Expert laboratory and clinical researchers from around the world review how to design and evaluate studies of tumor markers and examine their use in breast cancer patients. The authors cover both the major advances in sophisticated molecular methods and the state-of-the-art in conventional prognostic and predictive indicators. Among the topics discussed are the relevance of rigorous study design and guidelines for the validation studies of new biomarkers, gene expression profiling by tissue microarrays, adjuvant systemic therapy, and the use of estrogen, progesterone, and epidermal growth factor receptors as both prognostic and predictive indicators. Highlights include the evaluation of HER2 and EGFR family members, of p53, and of UPA/PAI-1; the detection of rare cells in blood and marrow; and the detection and analysis of soluble, circulating markers.

Trends in Breast Cancer Prevention

Author : Jose Russo
Publisher : Springer
ISBN 13 : 3319271350
Total Pages : 296 pages
Book Rating : 4.3/5 (192 download)

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Book Synopsis Trends in Breast Cancer Prevention by : Jose Russo

Download or read book Trends in Breast Cancer Prevention written by Jose Russo and published by Springer. This book was released on 2016-07-14 with total page 296 pages. Available in PDF, EPUB and Kindle. Book excerpt: This volume, with contributions from the most recognized experts in preventive strategies in breast cancer, presents the accepted as well as the novel ideas that have been introduced for the prevention of breast cancer. There is no single preventive agent that can stop the incidence of breast cancer—the malignant disease most frequently diagnosed in women of all races and nationalities. Furthermore, its incidence around the globe is increasing in industrialized countries. The worldwide incidence of breast cancer has increased 30-40% since the 1970s, reaching an excess of 1,390,000 new cases and a mortality of more than 460,000 cases in 2015. Therefore, what is needed is the development of rational strategies for the prevention of this fatal disease.

Regulatory Mechanisms in Breast Cancer

Author : Marc E. Lippman
Publisher : Springer Science & Business Media
ISBN 13 : 1461539404
Total Pages : 455 pages
Book Rating : 4.4/5 (615 download)

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Book Synopsis Regulatory Mechanisms in Breast Cancer by : Marc E. Lippman

Download or read book Regulatory Mechanisms in Breast Cancer written by Marc E. Lippman and published by Springer Science & Business Media. This book was released on 2012-12-06 with total page 455 pages. Available in PDF, EPUB and Kindle. Book excerpt: In Breast Cancer: Cellular and Molecular Biology [Kluwer Academic Pub lishers, 1988], we tried to present an introduction to the emerging basic studies on steroid receptors, oncogenes, and growth factors in the regulation of normal and malignant mammary epithelium. The response to this volume was superb, indicating a tremendous interest in basic growth regulatory mechanisms governing breast cancer and controlling its malignant progres sion. In the two years since its publication, much new and exciting in formation has been published and the full interplay of regulatory mechanisms is now beginning to emerge. We have divided this book into four sections that we hope will unify important concepts and help to crystallize areas of consensus and/or disagreement among a diverse group of basic and clinical scientists working on the disease. The first section is devoted to studies on oncogenes, antioncogenes, proliferation, and tumor prognosis. The first chapter, by Sunderland and McGuire, introduces the characteristics of breast cancer as studied by patho logists to establish prognostic outcome. Of particular interest is a new proto oncogene called HER-2 (or neu), which is rapidly becoming accepted as a valuable new tumor marker of poor prognosis. The second chapter, by Lee Bookstein and Lee, introduces the best known antioncogene, the retinoblas toma antioncogene, whose expression is sometimes lost in breast cancer. Malignant progression appears to be influenced by the balance of proto oncogene and antioncogene expression.

Estrogen and Aryl Hydrocarbon Receptor Signaling

Author : Elin Swedenborg
Publisher :
ISBN 13 : 9789174095296
Total Pages : 41 pages
Book Rating : 4.0/5 (952 download)

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Book Synopsis Estrogen and Aryl Hydrocarbon Receptor Signaling by : Elin Swedenborg

Download or read book Estrogen and Aryl Hydrocarbon Receptor Signaling written by Elin Swedenborg and published by . This book was released on 2009 with total page 41 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Mechanisms of Estrogen Receptor (ER) Action in Breast Cancer Cells

Author : Bradley Martin Saville
Publisher :
ISBN 13 :
Total Pages : 658 pages
Book Rating : 4.:/5 (517 download)

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Book Synopsis Mechanisms of Estrogen Receptor (ER) Action in Breast Cancer Cells by : Bradley Martin Saville

Download or read book Mechanisms of Estrogen Receptor (ER) Action in Breast Cancer Cells written by Bradley Martin Saville and published by . This book was released on 2002 with total page 658 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Mechanisms of Transcriptional Activation of Estrogen Responsive Genes in Breast Cancer Cells

Author : Chien-Cheng Chen
Publisher :
ISBN 13 :
Total Pages : pages
Book Rating : 4.:/5 (69 download)

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Book Synopsis Mechanisms of Transcriptional Activation of Estrogen Responsive Genes in Breast Cancer Cells by : Chien-Cheng Chen

Download or read book Mechanisms of Transcriptional Activation of Estrogen Responsive Genes in Breast Cancer Cells written by Chien-Cheng Chen and published by . This book was released on 2010 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: Estrogen receptor (ER) acts as a ligand-activated transcription factor that regulates the expression of genes. The genomic mechanisms of ER action include ligand-induced dimerization of ER which binds estrogen responsive elements (EREs) in the promoters of target genes. There are also nongenomic mechanisms of ER action which are associated with membrane bound or cytosol ER-dependent activation of various protein-kinase cascades which also influence expression of target genes. Egr-1 is an immediate-early gene induced by 17B-estradiol (E2) in the rodent uterus and breast cancer cells. Deletion analysis of the Egr-1 promoter identified a minimal E2-responsive region that contained serum response element (SRE3) which bound Elk-1 and serum response factor (SRF) in gel mobility shift assays. Hormone-responsiveness of Egr-1 in MCF-7 cells was specifically inhibited by PD98059, a MAPKK inhibitor, but not by LY294002, an inhibitor of PI3-K. These results contrasted with the hormone-dependent activation of the SRE in the c-fos promoter, which was inhibited by both PD98059 and LY294002, suggesting that Egr-1, like c-fos, is activated through non-genomic pathways of estrogen action but through activation of different kinases. COUP-TFs are orphan nuclear receptors expressed in a variety of tissues where they regulate biological functions and organogenesis. In this study, we investigated coactivation of ERa by COUP-TF1 in cell lines transiently cotransfected with the pERE3 construct. COUP-TFI coactivated ERał-mediated transactivation, but unlike many other coactivators, COUP-TFI also enhanced transactivation of ERa when cells were cotransfected with the TAF1-ERa mutant or the 19c-ERa mutant. These data indicate that helix 12 of ERa is not required for coactivation by COUP-TFI when AF-1 of ERa is intact. However, when the AF-1 of ERa is deleted, the intact AF-2 function is required for coactivation by COUP-TFI. Analysis of multiple COUP-TFI deletion mutants showed that the DNA-binding domain and C-terminal region of COUP-TFI were important for coactivation of ERa. Point mutations of the DNA-binding domain of COUP-TFI resulted in loss of interactions with ERa, suggesting that the DNA-binding domain of COUP-TFI is important for its coactivation activity facilitating interactions with ERa. These results demonstrate that COUP-TFI coactivated ERa through a non-classical LXXLL-independent pathway.

Estrogen Action, Selective Estrogen Receptor Modulators And Women's Health: Progress And Promise

Author : V Craig Jordan
Publisher : World Scientific
ISBN 13 : 1848169590
Total Pages : 544 pages
Book Rating : 4.8/5 (481 download)

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Book Synopsis Estrogen Action, Selective Estrogen Receptor Modulators And Women's Health: Progress And Promise by : V Craig Jordan

Download or read book Estrogen Action, Selective Estrogen Receptor Modulators And Women's Health: Progress And Promise written by V Craig Jordan and published by World Scientific. This book was released on 2013-05-27 with total page 544 pages. Available in PDF, EPUB and Kindle. Book excerpt: This volume presents the evolution of the authors' ideas about estrogen action and its modulation by a new group of drugs called SERMs (Selective Estrogen Receptor Modulators). The pioneering SERMs — tamoxifen and raloxifene — are known to have saved the lives of millions of women around the world and improved the health of millions more. Estrogen is the central hormone of women's health and reproduction. The book is a journey through 40 years of discovery and success in advancing women's health, with the prospect of improved innovation through medicinal chemistry for the future.

Aryl Hydrocarbon and Estrogen Receptor Alpha Crosstalk in Human Breast and Endometrial Cancer Cell Lines

Author : Mark Thomas Wormke
Publisher :
ISBN 13 :
Total Pages : 476 pages
Book Rating : 4.:/5 (527 download)

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Book Synopsis Aryl Hydrocarbon and Estrogen Receptor Alpha Crosstalk in Human Breast and Endometrial Cancer Cell Lines by : Mark Thomas Wormke

Download or read book Aryl Hydrocarbon and Estrogen Receptor Alpha Crosstalk in Human Breast and Endometrial Cancer Cell Lines written by Mark Thomas Wormke and published by . This book was released on 2002 with total page 476 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Mechanism of Environmental Carcinogen-Induced Mammary Tumorigenesis

Author : Zhi-Xiong J. Xiao
Publisher :
ISBN 13 :
Total Pages : 16 pages
Book Rating : 4.:/5 (227 download)

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Book Synopsis Mechanism of Environmental Carcinogen-Induced Mammary Tumorigenesis by : Zhi-Xiong J. Xiao

Download or read book Mechanism of Environmental Carcinogen-Induced Mammary Tumorigenesis written by Zhi-Xiong J. Xiao and published by . This book was released on 1999 with total page 16 pages. Available in PDF, EPUB and Kindle. Book excerpt: Environmental pollutants such as polycyclic aromatic hydrocarbons (PAH) are believed to contribute to the recent increase in breast cancer incidence and mortality. Yet, the molecular mechanism is poorly understood. In this study, we use a carcinogen-induced breast cancer animal model in which the female Sprague-Dawley (S-D) rats develop mammary tumors after a single intragastric dose of treatment of 7,1 2-dimethylbenz(a)anthracene (DMBA), a member of the PAM family. Estrogen is indispensable for the DMBA-mediated mammary tumorigenesis. We hypothesize that DMBA and estrogen receptor (ER) cooperate in activation of protooncogene Mdm2 which is important for DMBA-rat mammary tumorigenesis. We have confirmed that MDM2 is indeed overproduced in DMBA-mammary tumors, likely via a post-transcriptional mechanism(s). Analysis using the Rat cDNA Expression Array indicates an up-regulation of p450, as expected, as well as the down regulation of IGFl, IGF1R, c-Myc and JNK in the DMBA-treated mammary glands at an early stage of the DMBA treatment. We have also found a clear correlation between MDM2 expression and the status of the aromatic hydrocarbon receptor (AhR) and ER in a number of human breast cancer cells. MDM2 expression in MCF-7 cells is activated in a DMBA dose- and time-dependent manner. We show that at least two cellular proteins can specifically interact with an AhR site in MDM2 5' UTR. We conclude that overproduction of MDM2 may play a pathological role in carcinogen-induced mammary tumorigenesis and that MDM2 is upregulated by AhR and ER independent of p53 action.

Cross-talk Between Hormone-regulated Transcription Factors, STAT5b and ER, and Xenochemical Receptors, PPAR and AhR

Author : Jonathan M. Shipley
Publisher :
ISBN 13 :
Total Pages : 428 pages
Book Rating : 4.:/5 (298 download)

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Book Synopsis Cross-talk Between Hormone-regulated Transcription Factors, STAT5b and ER, and Xenochemical Receptors, PPAR and AhR by : Jonathan M. Shipley

Download or read book Cross-talk Between Hormone-regulated Transcription Factors, STAT5b and ER, and Xenochemical Receptors, PPAR and AhR written by Jonathan M. Shipley and published by . This book was released on 2005 with total page 428 pages. Available in PDF, EPUB and Kindle. Book excerpt: Abstract: Nuclear receptors are ligand-inducible transcription factors that bind to DNA-response elements of target genes as monomers, homodimers, or as heterodimers with the retinoid X receptor. Two members of the nuclear receptor superfamily are peroxisome proliferator activated receptors (PPAR) and the estrogen receptor (ER). JAK-STAT signaling is activated by multiple cytokines and hormones, including growth hormone (GH), and leads to the translocation of dimerized STAT proteins to the nucleus where they activate transcription of target genes. Previous studies have demonstrated that STAT5b can inhibit PPAR-regulated transcription. Herein this inhibitory cross-talk is shown to be mutual, and that GH-induced, STAT5b-regulated, luciferase reporter gene transcription is inhibited up to 80% by ligand-activated PPAR. Mechanistic studies characterize aspects of PPAR/STAT5b cross-talk, including the effect of PPAR on STAT5b protein levels and DNA-binding activity, as well as the role of specific PPAR protein domains. A PPAR-activated Renilla luciferase reporter plasmid was constructed and used in combination with a STAT5b firefly luciferase reporter to show that in cells co-stimulated with GH and a PPAR agonist, STAT5b inhibition of PPAR-regulated transcription occurs simultaneous with PPAR inhibition of STAT5b-regulated transcription. Another example of cross-talk involving a nuclear receptor is aryl hydrocarbon receptor (AhR) inhibition of ER-regulated transcription. Recent studies have demonstrated a pro-estrogenic action of the AhR that proceeds via the formation of an (AhR-Arnt)-ER complex, which binds to estrogen response elements (EREs) and stimulates transcription of ER target genes. Activation by the AhR ligand, 3-methylcholanthrene (3MC), of an ER-regulated luciferase reporter and ER target genes in the breast cancer cell line MCF-7 is demonstrated. ER reporter activity is additionally activated by 3MC in the AhR-positive mouse hepatoma 5L cell line and its AhR-negative variant BP8. The ability of 3MC to activate ER-regulated transcription in the absence of AhR suggests that this AhR ligand may activate ER directly, instead of, or in addition to, the AhR-dependent mechanism proposed. Together, these studies elucidate mechanisms through which the xenochemical receptors PPAR and AhR may respectively exert crosstalk with hormone-activated signaling pathways involving STAT5b and ER.