Koong-Dissertationdoctoral

Total Page:16

File Type:pdf, Size:1020Kb

Koong-Dissertationdoctoral Copyright by Luke Yun-Kong Koong 2014 The Dissertation Committee for Luke Yun-Kong Koong Certifies that this is the approved version of the following dissertation: THE DIRECT EFFECTS OF ESTRADIOL AND SEVERAL XENOESTROGENS ON CELL NUMBERS OF EARLY- VS. LATE- STAGE PROSTATE CANCER CELLS Committee: Cheryl S Watson, PhD, Mentor Darren Boehning, PhD, Chair Gracie Vargas, PhD Randall M Goldblum, MD Nancy Ing, DVM, PhD _______________________________ Dean, Graduate School THE DIRECT EFFECTS OF ESTRADIOL AND SEVERAL XENOESTROGENS ON CELL NUMBERS OF EARLY- VS. LATE- STAGE PROSTATE CANCER CELLS by Luke Yun-Kong Koong, BS Dissertation Presented to the Faculty of the Graduate School of The University of Texas Medical Branch in Partial Fulfillment of the Requirements for the Degree of Doctor of Philosophy The University of Texas Medical Branch December, 2014 Dedication This dissertation is dedicated to my family, whom has supported me with love and encouragement throughout my life; my friends, who push me to greater heights; and most importantly God, who continues to bless me every day with life and joy. Acknowledgements I would like to acknowledge my mentor, Cheryl S Watson, who has guided me through my graduate work. She has shown me how to be a true scientist and a responsible steward of our environment. I am forever grateful for the avenues she has opened up for my life and career. Additionally, I would like to thank my committee members for all of their constructive ideas throughout my project, as well as encouragement along the way. Another key figure in my graduate career is Jennifer Jeng of the Watson laboratory, who helped teach me many of the assays used in this study, and who was also available for advice and suggestions. The National Institutes of Environmental Health Sciences (NIEHS) Environmental Toxicology Training Grant helped me acquire numerous skills toward my career, as well as monetary support, and for that I am truly grateful. Finally, I want to acknowledge the GSBS and the support they provided me in finishing my degree. This work was supported by the NIEHS T32ES007254 Environmental Toxicology Training Grant. iv THE DIRECT EFFECTS OF ESTRADIOL AND SEVERAL XENOESTROGENS ON CELL NUMBERS OF EARLY- VS. LATE- STAGE PROSTATE CANCER CELLS Publication No._____________ Luke Yun-Kong Koong, PhD The University of Texas Medical Branch, 2014 Supervisor: Cheryl S Watson Prostate cancer is the most common non-cutaneous cancer among men, and diethylstilbestrol (DES) is an estrogen that has been used clinically to combat advanced tumors. Estrogens can indirectly decrease androgen production by central negative feedback inhibition, but may also have direct tumor killing mechanisms by a less well understood mechanism. To elucidate these mechanisms and provide understanding for potential future therapies, we identified cellular pathways and rapid signaling events that act via estrogen receptors (ERs) and contribute to estradiol (E2) or DES-mediated cell killing/growth arrest. E2 was much more effective than DES at reducing cell numbers of both LAPC-4 early-stage androgen-dependent and PC-3 late-stage androgen-independent prostate cancer cells. Both E2 and DES rapidly (within minutes) activated mitogen- activated protein kinases, generated reactive oxygen species (ROS), induced apoptosis and necroptosis, and regulated the activation and levels of cell cycle proteins. Regulation of cyclin D1 played a major role in blocking cell proliferation, but extracellular signal- v regulated kinase (ERK) causing ROS generation, phosphorylation of p38, apoptosis, and phosphorylation of p16INK4A also contributed. Our rapid effects suggested the participation of membrane ERs (mERs). ERα and β mediated E2’s ability to increase ROS through sustained ERK activation, and increased p-cyclin D1 levels in LAPC-4 cells. However, ERβ and GPR30 mediated these responses in PC-3 cells. Apoptosis was initiated in LAPC-4 and PC-3 cells by E2 only, and not by DES. Necroptosis was not altered by estrogens in either cell line. We showed for the first time the presence of mERs in both early and late prostate cancer cells. Then several xenoestrogens (XEs) were evaluated for their ability to increase or decrease prostate cancer cell numbers. Coumesterol and genistein unexpectedly stimulated prostate cancer cell growth, while resveratrol minimally increased cell numbers in both early and late-stage cells. Bisphenol A (BPA) slightly, though significantly, increased cell numbers in LAPC-4 cells only. Again, control of cyclin D1 protein levels was a key mediator of the growth change effects. The findings of these studies should be relevant to the clinical treatment of prostate tumors, including development of ER subtype-specific agents to control proliferation and cell death signaling pathways. Our findings regarding XEs should help establish guidelines for prostate cancer patients regarding consumption of safe dietary concentrations of phytoestrogens and acceptable exposure levels to BPA. vi TABLE OF CONTENTS List of Tables .............................................................................................................ix List of Figures ............................................................................................................x List of Abbreviations .................................................................................................xiii Chapter 1: Introduction ..............................................................................................15 Prostate tumors and methods of treatment ........................................................15 Prostate function and anatomy ..........................................................................17 Prostate cancer treatment regimens ..................................................................22 Development of androgen-independent tumors ................................................24 Estrogens and estrogen receptor physiology ....................................................27 Roles of membrane estrogen receptors in nongenomic responses ...................31 Estrogen receptor control of cell proliferation or death ....................................33 Estrogen receptors in the prostate and prostatic disease ...................................34 Xenoestrogens and effects on living systems ...................................................35 Aims of studies in this dissertation ...................................................................37 Aim 1 .......................................................................................................37 Aim 2 .......................................................................................................38 Chapter 2: Direct estradiol and diethylstilbestrol actions on early- vs. late-stage prostate cancer cells ..........................................................................................39 Abstract .............................................................................................................39 Introduction .......................................................................................................40 Materials and Methods......................................................................................43 Results ...............................................................................................................46 Discussion .........................................................................................................58 Conclusions .......................................................................................................63 Chapter 3: Rapid, nongenomic signaling effects of several xenoestrogens involved in early- vs. late-stage prostate cancer cell proliferation ......................................64 Abstract .............................................................................................................64 Introduction .......................................................................................................65 Materials and Methods......................................................................................68 vii Results and Discussion .....................................................................................72 Conclusions .......................................................................................................84 Chapter 4: Conclusions and Future Directions ..........................................................87 Major Conclusions from Our Studies ...............................................................87 In vivo model ....................................................................................................90 Receptor targeted agonists (Acadia ERβ agonists) ...........................................94 Other potential studies and directions ...............................................................96 References ..................................................................................................................99 Vita 154 viii List of Tables Table 2.1. Summary of mechanisms contributing to estrogen-induced decline in numbers of LAPC-4 or PC-3 prostate cancer cells. .........................60 ix List of Figures Figure 1.1. Functional domains of AR. ..................................................................19 Figure 1.2. Canonical AR signaling pathway. .......................................................21 Figure 1.3. Summary of roles for membrane and intracellular ERs. .................28 Figure 1.4. ERα and
Recommended publications
  • Clomifene Citrate(BANM, Rinnm) ⊗
    2086 Sex Hormones and their Modulators Profasi; UK: Choragon; Ovitrelle; Pregnyl; USA: Chorex†; Choron; Gonic; who received the drug for a shorter period.6 No association be- 8. Werler MM, et al. Ovulation induction and risk of neural tube Novarel; Ovidrel; Pregnyl; Profasi; Venez.: Ovidrel; Pregnyl; Profasi†. tween gonadotrophin therapy and ovarian cancer was noted in defects. Lancet 1994; 344: 445–6. Multi-ingredient: Ger.: NeyNormin N (Revitorgan-Dilutionen N Nr this study. The conclusions of this study were only tentative, 9. Greenland S, Ackerman DL. Clomiphene citrate and neural tube 65)†; Mex.: Gonakor. defects: a pooled analysis of controlled epidemiologic studies since the numbers who developed ovarian cancer were small; it and recommendations for future studies. Fertil Steril 1995; 64: has been pointed out that a successfully achieved pregnancy may 936–41. reduce the risk of some other cancers, and that the risks and ben- 10. Whiteman D, et al. Reproductive factors, subfertility, and risk efits of the procedure are not easy to balance.7 A review8 of epi- of neural tube defects: a case-control study based on the Oxford Clomifene Citrate (BANM, rINNM) ⊗ Record Linkage Study Register. Am J Epidemiol 2000; 152: demiological and cohort studies concluded that clomifene was 823–8. Chloramiphene Citrate; Citrato de clomifeno; Clomifène, citrate not associated with any increase in the risk of ovarian cancer 11. Sørensen HT, et al. Use of clomifene during early pregnancy de; Clomifeni citras; Clomiphene Citrate (USAN); Klomifeenisi- when used for less than 12 cycles, but noted conflicting results, and risk of hypospadias: population based case-control study.
    [Show full text]
  • Chemical Compounds As Carcinogenic Agents Second Supplementary Report: Literature of 1938 and 1939 Biological Considerations
    CHEMICAL COMPOUNDS AS CARCINOGENIC AGENTS SECONDSUPPLEMENTARY REPORT: LITERATURE OF 1938 AND 1939 J. W. COOK AND E. L. KENNAWAY (From the Royal Cancer Hospital (Free), London, and the University of Glasgow) BIOLOGICALCONSIDERATIONS (Continued from page 428, Jitly 1940) II. Action of Carcinogenic Compounds in Difierent Species and Tissues A number of reports of the action of carcinogenic compounds on human tis- sues have appeared. Klar (601) developed a nodule on the forearm after completion of a series of experiments with 3:4-benzpyrene. He applied a solution of the hydrocarbon (0.25 per cent in benzol) to the skin of mice with a paint brush and for at least part of the period wore rubber gloves. He also conducted experiments, of which no description is given, with the powdered hydrocarbon contained in a glass vessel. Three months after the completion of the experiments a small nodule appeared on the dorsum of the left forearm, This was excised in May 1938 and described by Professor Huckel as a “ so- called benign calcifying epithelioma.” The growth extended into the subcu- taneous fatty tissue; the connection with the superficial epithelium is not described nor is it evident in the two photomicrographs which illustrate the report. The author does not state his age. Gordonoff and Walthard (562) record the occurrence of a tumor in a labo- ratory assistant, aged forty-two, engaged in applying methylcholanthrene (0.3 per cent in benzol) to the skin of mice. The site was in the nasolabial fold, at a spot often touched by the patient when smoking. The microscopic ap- pearance was that of a “ still well delimited stage of an incipient squamous- cell sarcoma.” Cottini and Mazzone (479) deliberately applied 3 :4-benzpyrene ( 1 per cent in benzene) to the skin, generally of the arm or thigh, of 26 patients with various cutaneous diseases, usually daily for periods up to 120 days.
    [Show full text]
  • The Reactivity of Human and Equine Estrogen Quinones Towards Purine Nucleosides
    S S symmetry Article The Reactivity of Human and Equine Estrogen Quinones towards Purine Nucleosides Zsolt Benedek †, Peter Girnt † and Julianna Olah * Department of Inorganic and Analytical Chemistry, Budapest University of Technology and Economics, Szent Gellért tér 4, H-1111 Budapest, Hungary; [email protected] (Z.B.); [email protected] (P.G.) * Correspondence: [email protected] † These authors contributed equally to this work. Abstract: Conjugated estrogen medicines, which are produced from the urine of pregnant mares for the purpose of menopausal hormone replacement therapy (HRT), contain the sulfate conjugates of estrone, equilin, and equilenin in varying proportions. The latter three steroid sex hormones are highly similar in molecular structure as they only differ in the degree of unsaturation of the sterane ring “B”: the cyclohexene ring in estrone (which is naturally present in both humans and horses) is replaced by more symmetrical cyclohexadiene and benzene rings in the horse-specific (“equine”) hormones equilin and equilenin, respectively. Though the structure of ring “B” has only moderate influence on the estrogenic activity desired in HRT, it might still significantly affect the reactivity in potential carcinogenic pathways. In the present theoretical study, we focus on the interaction of estrogen orthoquinones, formed upon metabolic oxidation of estrogens in breast cells with purine nucleosides. This multistep process results in a purine base loss in the DNA chain (depurination) and the formation of a “depurinating adduct” from the quinone and the base. The point mutations induced in this manner are suggested to manifest in breast cancer development in the long run.
    [Show full text]
  • Materializing Estrogen and Regulation Under Canada's Food and Drugs Act, 1939-1953 Lara Jessie Tessaro
    Osgoode Hall Law School of York University Osgoode Digital Commons LLM Theses Theses and Dissertations 8-27-2018 Toxic Enactments: Materializing Estrogen and Regulation Under Canada's Food and Drugs Act, 1939-1953 Lara Jessie Tessaro Follow this and additional works at: https://digitalcommons.osgoode.yorku.ca/llm Part of the Legal History Commons TOXIC ENACTMENTS: MATERIALIZING ESTROGEN AND REGULATION UNDER CANADA’S FOOD AND DRUGS ACT, 1939-1953 LARA TESSARO A THESIS SUBMITTED TO THE FACULTY OF GRADUATE STUDIES IN PARTIAL FULFILLMENT OF THE REQUIREMENTS FOR THE DEGREE OF MASTER OF LAWS GRADUATE PROGRAM IN LAW OSGOODE HALL LAW SCHOOL, YORK UNIVERSITY TORONTO, ONTARIO August 2018 © Lara Tessaro, 2018 ABSTRACT The study describes how estrogen was standardized in Canada, in the 1940s and early 1950s, under the Food and Drugs Act. Contributing to interdisciplinary conversations, it provides an empirical case of how regulatory practices enact material realities. Using archival material, the study describes how estrogen was achieved, in part, through heterogeneous practices of the Canadian Committee on Pharmacopoeial Standards, National Health, and government solicitors. These regulators disagreed on whether, how, and by whom estrogens should be standardized. Rather than resolve these disagreements, Canada enacted multiple regulations purporting to standardize estrogen, and government solicitors practiced “techniques of validating” to render the regulations as lawful. I argue that these regulatory enactments materialized estrogen as a potent, unpredictable, and multiple object. Further, I show how estrogen spawned novel regulatory techniques in Canada, particularly the use of consumer product labels. In this way, estrogen catalyzed an early example of risk regulation in Canada.
    [Show full text]
  • Pp375-430-Annex 1.Qxd
    ANNEX 1 CHEMICAL AND PHYSICAL DATA ON COMPOUNDS USED IN COMBINED ESTROGEN–PROGESTOGEN CONTRACEPTIVES AND HORMONAL MENOPAUSAL THERAPY Annex 1 describes the chemical and physical data, technical products, trends in produc- tion by region and uses of estrogens and progestogens in combined estrogen–progestogen contraceptives and hormonal menopausal therapy. Estrogens and progestogens are listed separately in alphabetical order. Trade names for these compounds alone and in combination are given in Annexes 2–4. Sales are listed according to the regions designated by WHO. These are: Africa: Algeria, Angola, Benin, Botswana, Burkina Faso, Burundi, Cameroon, Cape Verde, Central African Republic, Chad, Comoros, Congo, Côte d'Ivoire, Democratic Republic of the Congo, Equatorial Guinea, Eritrea, Ethiopia, Gabon, Gambia, Ghana, Guinea, Guinea-Bissau, Kenya, Lesotho, Liberia, Madagascar, Malawi, Mali, Mauritania, Mauritius, Mozambique, Namibia, Niger, Nigeria, Rwanda, Sao Tome and Principe, Senegal, Seychelles, Sierra Leone, South Africa, Swaziland, Togo, Uganda, United Republic of Tanzania, Zambia and Zimbabwe America (North): Canada, Central America (Antigua and Barbuda, Bahamas, Barbados, Belize, Costa Rica, Cuba, Dominica, El Salvador, Grenada, Guatemala, Haiti, Honduras, Jamaica, Mexico, Nicaragua, Panama, Puerto Rico, Saint Kitts and Nevis, Saint Lucia, Saint Vincent and the Grenadines, Suriname, Trinidad and Tobago), United States of America America (South): Argentina, Bolivia, Brazil, Chile, Colombia, Dominican Republic, Ecuador, Guyana, Paraguay,
    [Show full text]
  • Recruited Mast Cells in the Tumor Microenvironment Enhance Bladder Cancer Metastasis Via Modulation of Erβ/CCL2/CCR2 EMT/MMP9 Signals
    www.impactjournals.com/oncotarget/ Oncotarget, Vol. 7, No. 7 Recruited mast cells in the tumor microenvironment enhance bladder cancer metastasis via modulation of ERβ/CCL2/CCR2 EMT/MMP9 signals Qun Rao1,2,3,*, Yuan Chen2,3,*, Chiuan-Ren Yeh3,*, Jie Ding3, Lei Li3, Chawnshang Chang3, Shuyuan Yeh3 1 Department of Gynaecology and Obstetrics, Tongji Medical College/Hospital, Huazhong University of Science and Technology, Wuhan, China 2 Sex Hormone Research Center, Department of Urology, Tongji Medical College/Hospital, Huazhong University of Science and Technology, Wuhan, China 3 George Whipple Lab for Cancer Research, Departments of Urology and Pathology, University of Rochester Medical Center, Rochester, NY, USA * These authors have contributed equally to this work Correspondence to: Shuyuan Yeh, e-mail: [email protected] Keywords: tumor associated immune cells, ERβ antagonist, oncology, carcinogenesis Received: April 06, 2015 Accepted: September 02, 2015 Published: November 05, 2015 ABSTRACT Early clinical studies suggested that infiltrating mast cells could be associated with a poor outcome in bladder cancer (BCa) patients. The mechanisms of how mast cells influence the BCa progression, however, are unclear. Using the human clinical BCa sample survey and in vitro co-culture systems, we found BCa cells could recruit more mast cells than the surrounding non-malignant urothelial cells. The consequences of this better recruitment of mast cells toward BCa cells could then enhance BCa cell invasion. Mechanism dissection revealed that the enhanced BCa cell invasion could function via up-regulation of the estrogen receptor beta (ERβ) in both mast cells and BCa cells, which resulted in the increased CCL2/CCR2/EMT/MMP9 signals.
    [Show full text]
  • Conjugated Estrogens Sustained Release Tablets) 0.3 Mg, 0.625 Mg, and 1.25 Mg
    PRODUCT MONOGRAPH PrPREMARIN® (conjugated estrogens sustained release tablets) 0.3 mg, 0.625 mg, and 1.25 mg ESTROGENIC HORMONES ® Wyeth Canada Date of Revision: Pfizer Canada Inc., Licensee December 1, 2014 17,300 Trans-Canada Highway Kirkland, Quebec H9J 2M5 Submission Control No: 177429 PREMARIN (conjugated estrogens sustained release tablets) Page 1 of 46 Table of Contents PART I: HEALTH PROFESSIONAL INFORMATION .........................................................3 SUMMARY PRODUCT INFORMATION ...........................................................................3 INDICATIONS AND CLINICAL USE ................................................................................3 CONTRAINDICATIONS ......................................................................................................4 WARNINGS AND PRECAUTIONS ....................................................................................4 ADVERSE REACTIONS ....................................................................................................14 DRUG INTERACTIONS ....................................................................................................20 DOSAGE AND ADMINISTRATION ................................................................................23 OVERDOSAGE ...................................................................................................................25 ACTION AND CLINICAL PHARMACOLOGY ...............................................................25 STORAGE AND STABILITY ............................................................................................28
    [Show full text]
  • Pharmaceutical and Veterinary Compounds and Metabolites
    PHARMACEUTICAL AND VETERINARY COMPOUNDS AND METABOLITES High quality reference materials for analytical testing of pharmaceutical and veterinary compounds and metabolites. lgcstandards.com/drehrenstorfer [email protected] LGC Quality | ISO 17034 | ISO/IEC 17025 | ISO 9001 PHARMACEUTICAL AND VETERINARY COMPOUNDS AND METABOLITES What you need to know Pharmaceutical and veterinary medicines are essential for To facilitate the fair trade of food, and to ensure a consistent human and animal welfare, but their use can leave residues and evidence-based approach to consumer protection across in both the food chain and the environment. In a 2019 survey the globe, the Codex Alimentarius Commission (“Codex”) was of EU member states, the European Food Safety Authority established in 1963. Codex is a joint agency of the FAO (Food (EFSA) found that the number one food safety concern was and Agriculture Office of the United Nations) and the WHO the misuse of antibiotics, hormones and steroids in farm (World Health Organisation). It is responsible for producing animals. This is, in part, related to the issue of growing antibiotic and maintaining the Codex Alimentarius: a compendium of resistance in humans as a result of their potential overuse in standards, guidelines and codes of practice relating to food animals. This level of concern and increasing awareness of safety. The legal framework for the authorisation, distribution the risks associated with veterinary residues entering the food and control of Veterinary Medicinal Products (VMPs) varies chain has led to many regulatory bodies increasing surveillance from country to country, but certain common principles activities for pharmaceutical and veterinary residues in food and apply which are described in the Codex guidelines.
    [Show full text]
  • Memory-Related Synaptic Plasticity Is Sexually Dimorphic in Rodent Hippocampus
    The Journal of Neuroscience, September 12, 2018 • 38(37):7935–7951 • 7935 Development/Plasticity/Repair Memory-Related Synaptic Plasticity Is Sexually Dimorphic in Rodent Hippocampus Weisheng Wang,1 Aliza A. Le,1 Bowen Hou,1 Julie C. Lauterborn,1 XConor D. Cox,1 Ellis R. Levin,2,5 Gary Lynch,1,3 and X Christine M. Gall1,4 Departments of 1Anatomy and Neurobiology, 2Medicine, 3Psychiatry and Human Behavior, 4Neurobiology and Behavior, University of California, Irvine, Irvine, California 92697, and 5Division of Endocrinology, Veterans Affairs Medical Center, Long Beach, California 90822 Men are generally superior to women in remembering spatial relationships, whereas the reverse holds for semantic information, but the neurobiological bases for these differences are not understood. Here we describe striking sexual dimorphism in synaptic mechanisms of memory encoding in hippocampal field CA1, a region critical for spatial learning. Studies of acute hippocampal slices from adult rats and mice show that for excitatory Schaffer–commissural projections, the memory-related long-term potentiation (LTP) effect depends upon endogenous estrogen and membrane estrogen receptor ␣ (ER␣) in females but not in males; there was no evident involvement of nuclear ER␣ in females, or of ER␤ or GPER1 (G-protein-coupled estrogen receptor 1) in either sex. Quantitative immunofluorescence showed that stimulation-induced activation of two LTP-related kinases (Src, ERK1/2), and of postsynaptic TrkB, required ER␣ in females only, and that postsynaptic ER␣ levels are higher in females than in males. Several downstream signaling events involved in LTP were comparable between the sexes. In contrast to endogenous estrogen effects, infused estradiol facilitated LTP and synaptic signaling in females via both ER␣ and ER␤.
    [Show full text]
  • Estriol Prevention of Mammary Carcinoma Induced by 7,12-Dimethylbenzanthracene and Procarbazine1
    (CANCER RESEARCH 35, 1341 1353, May 1975] Estriol Prevention of Mammary Carcinoma Induced by 7,12-Dimethylbenzanthracene and Procarbazine1 Henry M. Lemon Section of Oncology, Department of Internal Medicine, The University of Nebraska Medical Center, 42nd Street and Dewey Avenue, Omaha. Nebraska 68105 SUMMARY hexestrol, 0.60 mg/pellet, did not alter breast cancer incidence in 220 additional rats. Estrogen-treated rats The concentration of estrogenic, androgenic, progesta- usually sustained a mean 0.6 to 8.9% reduction of body tional, and adrenocortical steroid hormones in body fluids growth for the first 6 to 8 months of observation; this did of mature intact Sprague-Dawley female rats was increased not correlate with the breast carcinoma-suppressive activi by s.c. implantation of 5 to 7 mg NaCl pellets containing 1 ties of individual steroids. to 20% steroid 48 hr before administration p.o. of either Single implantation of 0.60 mg estriol 48 hr before 7,12-dimethylbenz(a)anthracene or procarbazine. The inci dimethylbenzanthracene p.o. or sustained implantation dence of rats developing one or more mammary carcinomas every 2 months of 10% estriol pellets beginning 24 hr after in each treated group was compared to that observed in si carcinogen exposure failed significantly to alter mammary multaneously treated groups receiving only the carcinogen, carcinoma development after dimethylben/anthracene ad steroid, or no treatment whatsoever, with weekly observa ministration. tion of all rats until palpably growing tumors were biopsied Inhibition of mammary carcinogenesis induced by these and proven carcinomatous or until death occurred from two dissimilar carcinogens in intact mature rats using other causes determined by autopsy.
    [Show full text]
  • Understanding the Dynamics of Toll-Like Receptor 5 Response to Flagellin and Its Regulation by Estradiol
    Understanding the dynamics of Toll-like Receptor 5 response to flagellin and its regulation by estradiol Ignacio Caballero-Posadas, James Boyd, Carmen Alminana-Brines, Javier A. Sánchez-López, Shaghayegh Basatvat, Mehrnaz Montazeri, Nasim Maslehat Lay, Sarah Elliott, David G. Spiller, Michael R. H. White, et al. To cite this version: Ignacio Caballero-Posadas, James Boyd, Carmen Alminana-Brines, Javier A. Sánchez-López, Shaghayegh Basatvat, et al.. Understanding the dynamics of Toll-like Receptor 5 response to flag- ellin and its regulation by estradiol. Scientific Reports, Nature Publishing Group, 2017, 7, 10p. 10.1038/srep40981. hal-01594679 HAL Id: hal-01594679 https://hal.archives-ouvertes.fr/hal-01594679 Submitted on 26 Sep 2017 HAL is a multi-disciplinary open access L’archive ouverte pluridisciplinaire HAL, est archive for the deposit and dissemination of sci- destinée au dépôt et à la diffusion de documents entific research documents, whether they are pub- scientifiques de niveau recherche, publiés ou non, lished or not. The documents may come from émanant des établissements d’enseignement et de teaching and research institutions in France or recherche français ou étrangers, des laboratoires abroad, or from public or private research centers. publics ou privés. Distributed under a Creative Commons Attribution| 4.0 International License www.nature.com/scientificreports OPEN Understanding the dynamics of Toll-like Receptor 5 response to flagellin and its regulation by Received: 16 September 2016 Accepted: 13 December 2016 estradiol Published: 23 January 2017 Ignacio Caballero1,2, James Boyd3, Carmen Almiñana1, Javier A. Sánchez-López1, Shaghayegh Basatvat1, Mehrnaz Montazeri1, Nasim Maslehat Lay1, Sarah Elliott1, David G.
    [Show full text]
  • Targeting Estrogen Receptor Subtypes (Era and Erb) with Selective ER Modulators in Ovarian Cancer
    KK-L CHAN and others Estrogen receptor subtypes in 221:2 325–336 Research ovarian cancer Targeting estrogen receptor subtypes (ERa and ERb) with selective ER modulators in ovarian cancer Karen Kar-Loen Chan, Thomas Ho-Yin Leung, David Wai Chan, Na Wei, Correspondence Grace Tak-Yi Lau, Stephanie Si Liu, Michelle K-Y Siu and Hextan Yuen-Sheung Ngan should be addressed to K K-L Chan Department of Obstetrics and Gynaecology, LKS Faculty of Medicine, The University of Hong Kong, Email 6/F Professorial Block, Queen Mary Hospital, Pokfulam, Hong Kong [email protected] Abstract Ovarian cancer cells express both estrogen receptor a (ERa) and ERb, and hormonal therapy is Key Words an attractive treatment option because of its relatively few side effects. However, estrogen " estrogen receptors was previously shown to have opposite effects in tumors expressing ERa compared with ERb, " SERMS indicating that the two receptor subtypes may have opposing effects. This may explain the " ovarian cancer modest response to nonselective estrogen inhibition in clinical practice. In this study, we " hormonal treatment aimed to investigate the effect of selectively targeting each ER subtype on ovarian cancer growth. Ovarian cancer cell lines SKOV3 and OV2008, expressing both ER subtypes, were treated with highly selective ER modulators. Sodium 30-(1-(phenylaminocarbonyl)-3,4- Journal of Endocrinology tetrazolium)-bis(4-methoxy-6-nitro) benzene sulfonic acid hydrate (XTT) assay revealed that treatment with 1,3-bis(4-hydroxyphenyl)-4-methyl-5-[4-(2-piperidinylethoxy)phenol]-1H- pyrazole dihydrochloride (MPP) (ERa antagonist) or 2,3-bis(4-hydroxy-phenyl)-propionitrile (DPN) (ERb agonist) significantly suppressed cell growth in both cell lines.
    [Show full text]