Progesterone Receptor Transcription and Non-Transcription Signaling Mechanisms Susan A
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RUNX1 Control of Mammary Epithelial and Breast Cancer Cell Phenotypes
University of Massachusetts Medical School eScholarship@UMMS GSBS Dissertations and Theses Graduate School of Biomedical Sciences 2017-12-12 RUNX1 Control of Mammary Epithelial and Breast Cancer Cell Phenotypes Deli Hong University of Massachusetts Medical School Let us know how access to this document benefits ou.y Follow this and additional works at: https://escholarship.umassmed.edu/gsbs_diss Part of the Cancer Biology Commons, and the Cell Biology Commons Repository Citation Hong D. (2017). RUNX1 Control of Mammary Epithelial and Breast Cancer Cell Phenotypes. GSBS Dissertations and Theses. https://doi.org/10.13028/M21Q2F. Retrieved from https://escholarship.umassmed.edu/gsbs_diss/949 This material is brought to you by eScholarship@UMMS. It has been accepted for inclusion in GSBS Dissertations and Theses by an authorized administrator of eScholarship@UMMS. For more information, please contact [email protected]. RUNX1 CONTROL OF MAMMARY EPITHELIAL AND BREAST CANCER CELL PHENOTYPES A Dissertation Presented By Deli Hong Submitted to the Faculty of the University of Massachusetts Graduate School of Biomedical Sciences, Worcester in partial fulfillment of the requirements for the degree of DOCTOR OF PHILOSOPHY December 12, 2017 Program of Cell Biology RUNX1 CONTROL OF MAMMARY EPITHELIAL AND BREAST CANCER CELL PHENOTYPES A Dissertation Presented By Deli Hong This work was undertaken in the Graduate School of Biomedical Sciences Program of Cell Biology The signature of the Thesis Advisor signifies validation of Dissertation content Gary S. Stein, Ph. D., Thesis Advisor The signatures of the Dissertation Defense Committee signify completion and approval as to style and content of the Dissertation Leslie Shaw, Ph. -
Jun Dimerization Protein 2 Activates Mc2r Transcriptional Activity: Role of Phosphorylation and Sumoylation
International Journal of Molecular Sciences Article Jun Dimerization Protein 2 Activates Mc2r Transcriptional Activity: Role of Phosphorylation and SUMOylation Chiung-Min Wang 1, Raymond X. Wang 1, Runhua Liu 2 and Wei-Hsiung Yang 1,* 1 Department of Biomedical Sciences, Mercer University School of Medicine, Savannah, GA 31404, USA; [email protected] (C.-M.W.); [email protected] (R.X.W.) 2 Department of Genetics and Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, AL 35294, USA; [email protected] * Correspondence: [email protected]; Tel.: +1-912-721-8203; Fax: +1-912-721-8268 Academic Editor: William Chi-shing Cho Received: 15 December 2016; Accepted: 26 January 2017; Published: 31 January 2017 Abstract: Jun dimerization protein 2 (JDP2), a basic leucine zipper transcription factor, is involved in numerous biological and cellular processes such as cancer development and regulation, cell-cycle regulation, skeletal muscle and osteoclast differentiation, progesterone receptor signaling, and antibacterial immunity. Though JDP2 is widely expressed in mammalian tissues, its function in gonads and adrenals (such as regulation of steroidogenesis and adrenal development) is largely unknown. Herein, we find that JDP2 mRNA and proteins are expressed in mouse adrenal gland tissues. Moreover, overexpression of JDP2 in Y1 mouse adrenocortical cancer cells increases the level of melanocortin 2 receptor (MC2R) protein. Notably, Mc2r promoter activity is activated by JDP2 in a dose-dependent manner. Next, by mapping the Mc2r promoter, we show that cAMP response elements (between −1320 and −720-bp) are mainly required for Mc2r activation by JDP2 and demonstrate that −830-bp is the major JDP2 binding site by real-time chromatin immunoprecipitation (ChIP) analysis. -
GATA3 As an Adjunct Prognostic Factor in Breast Cancer Patients with Less Aggressive Disease: a Study with a Review of the Literature
diagnostics Article GATA3 as an Adjunct Prognostic Factor in Breast Cancer Patients with Less Aggressive Disease: A Study with a Review of the Literature Patrizia Querzoli 1, Massimo Pedriali 1 , Rosa Rinaldi 2 , Paola Secchiero 3, Paolo Giorgi Rossi 4 and Elisabetta Kuhn 5,6,* 1 Section of Anatomic Pathology, Department of Morphology, Surgery and Experimental Medicine, University of Ferrara, 44124 Ferrara, Italy; [email protected] (P.Q.); [email protected] (M.P.) 2 Section of Anatomic Pathology, ASST Mantova, Ospedale Carlo Poma, 46100 Mantova, Italy; [email protected] 3 Surgery and Experimental Medicine and Interdepartmental Center of Technology of Advanced Therapies (LTTA), Department of Morphology, University of Ferrara, 44121 Ferrara, Italy; [email protected] 4 Epidemiology Unit, Azienda Unità Sanitaria Locale-IRCCS di Reggio Emilia, 42122 Reggio Emilia, Italy; [email protected] 5 Division of Pathology, Fondazione IRCCS Ca’ Granda, Ospedale Maggiore Policlinico, 20122 Milano, Italy 6 Department of Biomedical, Surgical, and Dental Sciences, University of Milan, 20122 Milano, Italy * Correspondence: [email protected]; Tel.: +39-02-5032-0564; Fax: +39-02-5503-2860 Abstract: Background: GATA binding protein 3 (GATA3) expression is positively correlated with Citation: Querzoli, P.; Pedriali, M.; estrogen receptor (ER) expression, but its prognostic value as an independent factor remains unclear. Rinaldi, R.; Secchiero, P.; Rossi, P.G.; Thus, we undertook the current study to evaluate the expression of GATA3 and its prognostic value Kuhn, E. GATA3 as an Adjunct in a large series of breast carcinomas (BCs) with long-term follow-up. Methods: A total of 702 Prognostic Factor in Breast Cancer consecutive primary invasive BCs resected between 1989 and 1993 in our institution were arranged Patients with Less Aggressive in tissue microarrays, immunostained for ER, progesterone receptor (PR), ki-67, HER2, p53, and Disease: A Study with a Review of GATA3, and scored. -
Pdgfb and P53 in Brain Tumorigenesis
From the Department of Oncology-Pathology Karolinska Institutet, Stockholm, Sweden PDGFB AND P53 IN BRAIN TUMORIGENESIS Sanna-Maria Hede Stockholm 2010 All previously published papers were reproduced with permission from the publisher. Published by Karolinska Institutet. Printed by Larserics Digital Print AB. © Sanna-Maria Hede, 2010 ISBN 978-91-7457-054-0 ABSTRACT Glioblastoma is the most common, and malignant form of brain tumor. It is characterized by a rapid growth and diffuse spread to surrounding brain tissue. The cell of origin is still not known, but experimental data suggest an origin from a glial precursor or neural stem cell. Analysis of human glioma tissue has revealed many genetic aberrations, among which mutations and loss of TP53 together with amplification and over-expression of PDGFRA are common. Many of the pathways that are found mutated in gliomas, are normally important in regulating stem cell functions. We have investigated the role of p53 in adult neural stem cells, and found that the p53 protein is expressed in the SVZ in mice. Comparison of neurosphere cultures derived from wt and Trp53-/- mice showed that neural stem cells lacking p53 have an increased self-renewal capacity, proliferate faster and display reduced apoptosis. Gene expression profiling revealed differential expression of many genes, the most prominent being Cdkn1a (p21) which was down-regulated in Trp53-/- neural stem cells. Mice lacking p53 do not develop gliomas, but the combination of TP53 mutation/deletion together with other genetic aberrations is common in human gliomas of all grades. We generated a transgenic mouse model mimicking human glioblastoma, by over-expressing PDGFB under the GFAP promoter in Trp53-/- mice. -
AP-1- Dependent Pathway Receptor, Focal
Peptidoglycan Enhances IL-6 Production in Human Synovial Fibroblasts via TLR2 Receptor, Focal Adhesion Kinase, Akt, and AP-1- Dependent Pathway This information is current as of September 25, 2021. Yung-Cheng Chiu, Ching-Yuang Lin, Chao-Ping Chen, Kui-Chou Huang, Kwok-Man Tong, Chung-Yuh Tzeng, Tu-Sheng Lee, Horng-Chaung Hsu and Chih-Hsin Tang J Immunol 2009; 183:2785-2792; Prepublished online 27 July 2009; Downloaded from doi: 10.4049/jimmunol.0802826 http://www.jimmunol.org/content/183/4/2785 http://www.jimmunol.org/ References This article cites 38 articles, 20 of which you can access for free at: http://www.jimmunol.org/content/183/4/2785.full#ref-list-1 Why The JI? Submit online. • Rapid Reviews! 30 days* from submission to initial decision • No Triage! Every submission reviewed by practicing scientists by guest on September 25, 2021 • Fast Publication! 4 weeks from acceptance to publication *average Subscription Information about subscribing to The Journal of Immunology is online at: http://jimmunol.org/subscription Permissions Submit copyright permission requests at: http://www.aai.org/About/Publications/JI/copyright.html Email Alerts Receive free email-alerts when new articles cite this article. Sign up at: http://jimmunol.org/alerts The Journal of Immunology is published twice each month by The American Association of Immunologists, Inc., 1451 Rockville Pike, Suite 650, Rockville, MD 20852 Copyright © 2009 by The American Association of Immunologists, Inc. All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. The Journal of Immunology Peptidoglycan Enhances IL-6 Production in Human Synovial Fibroblasts via TLR2 Receptor, Focal Adhesion Kinase, Akt, and AP-1- Dependent Pathway1 Yung-Cheng Chiu,*§¶ Ching-Yuang Lin,* Chao-Ping Chen,§ Kui-Chou Huang,§ Kwok-Man Tong,§ Chung-Yuh Tzeng,§ Tu-Sheng Lee,§ Horng-Chaung Hsu,2* and Chih-Hsin Tang2†‡ Peptidoglycan (PGN), the major component of the cell wall of Gram-positive bacteria, activates the innate immune system of the host and induces the release of cytokines and chemokines. -
Transcriptional Regulation by Extracellular Signals 209
Cell, Vol. 80, 199-211, January 27, 1995, Copyright © 1995 by Cell Press Transcriptional Regulation Review by Extracellular Signals: Mechanisms and Specificity Caroline S. Hill and Richard Treisman Nuclear Translocation Transcription Laboratory In principle, regulated nuclear localization of transcription Imperial Cancer Research Fund factors can involve regulated activity of either nuclear lo- Lincoln's Inn Fields calization signals (NLSs) or cytoplasmic retention signals, London WC2A 3PX although no well-characterized case of the latter has yet England been reported. N LS activity, which is generally dependent on short regions of basic amino acids, can be regulated either by masking mechanisms or by phosphorylations Changes in cell behavior induced by extracellular signal- within the NLS itself (Hunter and Karin, 1992). For exam- ing molecules such as growth factors and cytokines re- ple, association with an inhibitory subunit masks the NLS quire execution of a complex program of transcriptional of NF-KB and its relatives (Figure 1; for review see Beg events. While the route followed by the intracellular signal and Baldwin, 1993), while an intramolecular mechanism from the cell membrane to its transcription factor targets may mask NLS activity in the heat shock regulatory factor can be traced in an increasing number of cases, how the HSF2 (Sheldon and Kingston, 1993). When transcription specificity of the transcriptional response of the cell to factor localization is dependent on regulated NLS activity, different stimuli is determined is much less clear. How- linkage to a constitutively acting NLS may be sufficient to ever, it is possible to understand at least in principle how render nuclear localization independent of signaling (Beg different stimuli can activate the same signal pathway yet et al., 1992). -
Homeobox Gene Expression Profile in Human Hematopoietic Multipotent
Leukemia (2003) 17, 1157–1163 & 2003 Nature Publishing Group All rights reserved 0887-6924/03 $25.00 www.nature.com/leu Homeobox gene expression profile in human hematopoietic multipotent stem cells and T-cell progenitors: implications for human T-cell development T Taghon1, K Thys1, M De Smedt1, F Weerkamp2, FJT Staal2, J Plum1 and G Leclercq1 1Department of Clinical Chemistry, Microbiology and Immunology, Ghent University Hospital, Ghent, Belgium; and 2Department of Immunology, Erasmus Medical Center, Rotterdam, The Netherlands Class I homeobox (HOX) genes comprise a large family of implicated in this transformation proces.14 The HOX-C locus transcription factors that have been implicated in normal and has been primarily implicated in lymphomas.15 malignant hematopoiesis. However, data on their expression or function during T-cell development is limited. Using degener- Hematopoietic cells are derived from stem cells that reside in ated RT-PCR and Affymetrix microarray analysis, we analyzed fetal liver (FL) in the embryo and in the adult bone marrow the expression pattern of this gene family in human multipotent (ABM), which have the unique ability to self-renew and thereby stem cells from fetal liver (FL) and adult bone marrow (ABM), provide a life-long supply of blood cells. T lymphocytes are a and in T-cell progenitors from child thymus. We show that FL specific type of hematopoietic cells that play a major role in the and ABM stem cells are similar in terms of HOX gene immune system. They develop through a well-defined order of expression, but significant differences were observed between differentiation steps in the thymus.16 Several transcription these two cell types and child thymocytes. -
RANK Interaction and Signaling − RANKL Structural and Functional
Structural and Functional Insights of RANKL −RANK Interaction and Signaling Changzhen Liu, Thomas S. Walter, Peng Huang, Shiqian Zhang, Xuekai Zhu, Ying Wu, Lucy R. Wedderburn, Peifu This information is current as Tang, Raymond J. Owens, David I. Stuart, Jingshan Ren and of October 1, 2021. Bin Gao J Immunol published online 14 May 2010 http://www.jimmunol.org/content/early/2010/05/14/jimmun ol.0904033 Downloaded from Why The JI? Submit online. http://www.jimmunol.org/ • Rapid Reviews! 30 days* from submission to initial decision • No Triage! Every submission reviewed by practicing scientists • Fast Publication! 4 weeks from acceptance to publication *average Subscription Information about subscribing to The Journal of Immunology is online at: by guest on October 1, 2021 http://jimmunol.org/subscription Permissions Submit copyright permission requests at: http://www.aai.org/About/Publications/JI/copyright.html Email Alerts Receive free email-alerts when new articles cite this article. Sign up at: http://jimmunol.org/alerts The Journal of Immunology is published twice each month by The American Association of Immunologists, Inc., 1451 Rockville Pike, Suite 650, Rockville, MD 20852 All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. Published May 14, 2010, doi:10.4049/jimmunol.0904033 The Journal of Immunology Structural and Functional Insights of RANKL–RANK Interaction and Signaling Changzhen Liu,*,†,1 Thomas S. Walter,‡,1 Peng Huang,x Shiqian Zhang,{ Xuekai Zhu,*,† Ying Wu,*,† Lucy R. Wedderburn,‖ Peifu Tang,x Raymond J. Owens,‡ David I. Stuart,‡ Jingshan Ren,‡ and Bin Gao*,†,‖ Bone remodeling involves bone resorption by osteoclasts and synthesis by osteoblasts and is tightly regulated by the receptor activator of the NF-kB ligand (RANKL)/receptor activator of the NF-kB (RANK)/osteoprotegerin molecular triad. -
Progesterone Receptor Isoform B Regulates the Oxtr-Plcl2-Trpc3 Pathway to Suppress Uterine Contractility
Progesterone receptor isoform B regulates the Oxtr-Plcl2-Trpc3 pathway to suppress uterine contractility Mary C. Peaveya,1, San-Pin Wub,1, Rong Lib, Jian Liub, Olivia M. Emeryb, Tianyuan Wangc, Lecong Zhouc, Margeaux Wetendorfd, Chandra Yallampallie, William E. Gibbonse, John P. Lydond, and Francesco J. DeMayob,2 aDepartment of Obstetrics and Gynecology, University of North Carolina, Chapel Hill, NC 27599; bReproductive and Developmental Biology Laboratory, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709; cIntegrative Bioinformatic Support Group, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709; dDepartment of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030; and eDepartment of Obstetrics and Gynecology, Baylor College of Medicine, Houston, TX 77030 Edited by R. Michael Roberts, University of Missouri, Columbia, MO, and approved January 19, 2021 (received for review June 6, 2020) Uterine contractile dysfunction leads to pregnancy complications The “progesterone receptor isoform switch” concept was posited such as preterm birth and labor dystocia. In humans, it is hypoth- to explain the transition from a quiescent to a contractile myometrial esized that progesterone receptor isoform PGR-B promotes a re- phenotype in the presence of high levels of progesterone (10, 11, laxed state of the myometrium, and PGR-A facilitates uterine 26–30). Progesterone acts via the nuclear receptor isoforms, PGR-A contraction. This hypothesis was tested in vivo using transgenic and PGR-B, which are coexpressed at different levels throughout mouse models that overexpress PGR-A or PGR-B in smooth muscle pregnancy (31–35). Progesterone can transactivate different tran- cells. Elevated PGR-B abundance results in a marked increase in scriptional programs determined by the relative levels of PGR-A and gestational length compared to control mice (21.1 versus 19.1 d PGR-B isoforms in the myometrium (36–41). -
The Novel Progesterone Receptor
0013-7227/99/$03.00/0 Vol. 140, No. 3 Endocrinology Printed in U.S.A. Copyright © 1999 by The Endocrine Society The Novel Progesterone Receptor Antagonists RTI 3021– 012 and RTI 3021–022 Exhibit Complex Glucocorticoid Receptor Antagonist Activities: Implications for the Development of Dissociated Antiprogestins* B. L. WAGNER†, G. POLLIO, P. GIANGRANDE‡, J. C. WEBSTER, M. BRESLIN, D. E. MAIS, C. E. COOK, W. V. VEDECKIS, J. A. CIDLOWSKI, AND D. P. MCDONNELL Department of Pharmacology and Cancer Biology (B.L.W., G.P., P.G., D.P.M.), Duke University Medical Center, Durham, North Carolina 27710; Molecular Endocrinology Group (J.C.W., J.A.C.), NIEHS, National Institutes of Health, Research Triangle Park, North Carolina 27709; Department of Biochemistry and Molecular Biology (M.B., W.V.V.), Louisiana State University Medical School, New Orleans, Louisiana 70112; Ligand Pharmaceuticals, Inc. (D.E.M.), San Diego, California 92121; Research Triangle Institute (C.E.C.), Chemistry and Life Sciences, Research Triangle Park, North Carolina 27709 ABSTRACT by agonists for DNA response elements within target gene promoters. We have identified two novel compounds (RTI 3021–012 and RTI Accordingly, we observed that RU486, RTI 3021–012, and RTI 3021– 3021–022) that demonstrate similar affinities for human progeste- 022, when assayed for PR antagonist activity, accomplished both of rone receptor (PR) and display equivalent antiprogestenic activity. As these steps. Thus, all three compounds are “active antagonists” of PR with most antiprogestins, such as RU486, RTI 3021–012, and RTI function. When assayed on GR, however, RU486 alone functioned as 3021–022 also bind to the glucocorticoid receptor (GR) with high an active antagonist. -
860.Full.Pdf
Repression of IL-2 Promoter Activity by the Novel Basic Leucine Zipper p21 SNFT Protein This information is current as Milena Iacobelli, William Wachsman and Kathleen L. of September 29, 2021. McGuire J Immunol 2000; 165:860-868; ; doi: 10.4049/jimmunol.165.2.860 http://www.jimmunol.org/content/165/2/860 Downloaded from References This article cites 49 articles, 31 of which you can access for free at: http://www.jimmunol.org/content/165/2/860.full#ref-list-1 http://www.jimmunol.org/ Why The JI? Submit online. • Rapid Reviews! 30 days* from submission to initial decision • No Triage! Every submission reviewed by practicing scientists • Fast Publication! 4 weeks from acceptance to publication by guest on September 29, 2021 *average Subscription Information about subscribing to The Journal of Immunology is online at: http://jimmunol.org/subscription Permissions Submit copyright permission requests at: http://www.aai.org/About/Publications/JI/copyright.html Email Alerts Receive free email-alerts when new articles cite this article. Sign up at: http://jimmunol.org/alerts The Journal of Immunology is published twice each month by The American Association of Immunologists, Inc., 1451 Rockville Pike, Suite 650, Rockville, MD 20852 Copyright © 2000 by The American Association of Immunologists All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. Repression of IL-2 Promoter Activity by the Novel Basic Leucine Zipper p21SNFT Protein1,2 Milena Iacobelli,* William Wachsman,† and Kathleen L. McGuire3* IL-2 is the major autocrine and paracrine growth factor produced by T cells upon T cell stimulation. The inducible expression of IL-2 is highly regulated by multiple transcription factors, particularly AP-1, which coordinately activate the promoter. -
Pax6 During Visual System Development
Hedgehog-dependent E3-ligase Midline1 regulates ubiquitin-mediated proteasomal degradation of Pax6 during visual system development Thorsten Pfirrmanna,1, Enrico Jandta,1, Swantje Ranfta,b, Ashwin Lokapallya, Herbert Neuhausa, Muriel Perronc, and Thomas Hollemanna,2 aInstitute for Physiological Chemistry, University of Halle-Wittenberg, 06114 Halle, Germany; bGynecological Hospital, University Medical Center Mannheim, 68167 Mannheim, Germany; and cParis-Saclay Institute of Neuroscience, CNRS, Univ Paris Sud, Université Paris-Saclay, 91405 Orsay, France Edited by Richard M. Harland, University of California, Berkeley, CA, and approved July 19, 2016 (received for review January 16, 2016) Pax6 is a key transcription factor involved in eye, brain, and pancreas remains unclear how Pax6 protein is removed from the eyestalk development. Although pax6 is expressed in the whole prospective territory on time. Some authors report the regulation of Pax6 retinal field, subsequently its expression becomes restricted to the activity by posttranslational modifications (21–23), and most optic cup by reciprocal transcriptional repression of pax6 and pax2. interestingly, Tuoc et al. showed that in cortical progenitor cells, However, it remains unclear how Pax6 protein is removed from the Pax6 protein is degraded by the proteasome mediated by Trim11 eyestalk territory on time. Here, we report that Mid1, a member of (24). However, the existence of similar mechanisms leading to the RBCC/TRIM E3 ligase family, which was first identified in patients the development of the visual system is not known. with the X-chromosome–linked Opitz BBB/G (OS) syndrome, inter- The data of our present study show that Midline1 (Mid1) acts with Pax6. We found that the forming eyestalk is a major do- serves as one of these links.