DOCSLIB.ORG

Stromelysin-1 Regulates Adipogenesis During Mammary Gland Involution Caroline M

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Stromelysin-1 Regulates Adipogenesis During Mammary Gland Involution Caroline M View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by PubMed Central Stromelysin-1 Regulates Adipogenesis during Mammary Gland Involution Caroline M. Alexander,* Sushma Selvarajan,‡ John Mudgett,ʈ and Zena Werb§ *McArdle Laboratory for Cancer Research, University of Wisconsin Medical School, Madison, Wisconsin 53706-1599; ‡Department of Pharmaceutical Chemistry and §Department of Anatomy, University of California San Francisco, San Francisco, California 94143-0452; and ʈDepartment of Immunology, Merck Research Laboratory, Rahway, New Jersey 07065 Abstract. The matrix metalloproteinase MMP-3/stro- lial cell death after weaning, but instead alter the stro- melysin-1 (Str1) is highly expressed during mammary mal microenvironment. We used adipogenic 3T3-L1 gland involution induced by weaning. During involu- cells as a cell culture model to test the function of tion, programmed cell death of the secretory epithe- MMPs during adipocyte differentiation. Fibroblastic lium takes place concomitant with the repopulation of 3T3-L1 progenitor cells expressed very low levels of the mammary fat pad with adipocytes. In this study, we MMPs or TIMPs. The transcription of a number of have used a genetic approach to determine the role of MMP and TIMP mRNAs [Str1, MT1-MMP, (MMP-14) Str1 during mammary involution. Although Str1 has collagenase-3 (MMP-13), gelatinase A (MMP-2), and been shown to induce unscheduled apoptosis when ex- TIMP-1, -2 and -3] was induced in committed preadipo- pressed ectopically during late pregnancy (Alexander, cytes, but only differentiated adipocytes expressed an C.M., E.W. Howard, M.J. Bissell, and Z. Werb. 1996. J. activated MMP, gelatinase A. The addition of MMP in- Cell Biol. 135:1669–1677), we found that during post- hibitors (GM 6001 and TIMP-1) dramatically acceler- lactational involution, mammary glands from trans- ated the accumulation of lipid during differentiation. genic mice that overexpress the tissue inhibitor of me- We conclude that MMPs, especially Str1, determine the talloproteinases, TIMP-1 (TO), or mice carrying a targeted rate of adipocyte differentiation during involutive mutation in Str1 showed accelerated differentiation and mammary gland remodeling. hypertrophy of adipocytes, while epithelial apoptosis was unaffected. These data suggest that matrix metallo- Key words: transgenic mouse • mammary involution proteinases (MMPs) do not induce unscheduled epithe- • MMP-3 • TIMP-1 • 3T3-L1 adipocytes Introduction When pups are removed from a lactating mouse, the mam- or by altering cell cycle progression (Boudreau et al., 1995, mary glands involute, losing the expression of the differen- 1996; Wang et al., 1994; Wiesen and Werb, 2000). When tiated gene products associated with milk production and stromelysin-1 (Str1) is misexpressed in mammary gland by resulting in the loss of at least 90% of the lactating mam- transgenic means, mice show precocious growth of virgin mary epithelial cell number. Using this model of induced gland to a mid-pregnant equivalent (Sympson et al., 1994), apoptosis in adult mice, we can determine physiologically stromal alteration, and unscheduled apoptosis during relevant factors that control epithelial cell death. Mam- pregnancy (Boudreau et al., 1995; Alexander et al., 1996; mary gland involution is a two-phase process. The first Thomasset et al., 1998) and tumor formation (Sternlicht et phase is characterized by the onset of epithelial apoptosis, al., 1999). Therefore, we hypothesize that the response of which is p53 dependent (Jerry et al., 1998), and the second mammary epithelial cells to ectopic Str1 reflects normal phase by upregulation of proteinases, repopulation of the roles for this enzyme. mammary stroma by adipocytes, and completion of epi- The prototype MMP, collagenase, was isolated as a col- thelial programmed cell death in a p53-independent man- lagenolytic activity specifically induced during involution ner (Li et al., 1996; Lund et al., 1996). of the tadpole tail (Gross, 1966). Since the description of In cultured mammary epithelial cells, epithelial apopto- this activity, other MMPs have been shown to be induced sis is induced by expression of matrix metalloproteinases during physiological remodeling reactions and to cleave (MMPs),1 by the inhibition of integrin-mediated adhesion, structural proteins important to maintaining basement Address correspondence to Caroline M.Alexander, McArdle Laboratory 1Abbreviations used in this paper: dpc, days post coitum; ECM, extracellu- for Cancer Research, University of Wisconsin Medical School, 1400 Uni- lar matrix; H&E, hematoxylin and eosin; MMP, matrix metalloproteinase; versity Avenue, Madison, WI 53706-1599. Tel.: (608) 265 5182. Fax: (608) Str1, stromelysin-1/MMP-3; TIMP, tissue inhibitor of metalloproteinases; 262 2824. E-mail: [email protected] TO, TIMP overexpressing transgenic mouse; WAP, whey acidic protein. The Rockefeller University Press, 0021-9525/2001/02/693/11 $5.00 The Journal of Cell Biology, Volume 152, Number 4, February 19, 2001 693–703 http://www.jcb.org/cgi/content/full/152/4/693 693 membrane integrity (Sternlicht and Werb, 1999; Sternlicht moter have been described (Alexander et al., 1996). In brief, these mice ng/ml circulating human TIMP-1 50ف et al., 1999; Vu and Werb, 2000). One such MMP, Str1, is have no gross phenotype and express -ng/ml of tissue lysate from pregnant mammary gland. Mice carry 20ف and expressed and regulated during mammary gland develop- ing this transgene were compared with nontransgenic sibs or CD-1 control ment and involution (Witty et al., 1995). Str1 cleaves many mice (Charles River Laboratories). Mice carrying a targeted null mutation basement membrane proteins (Mayer et al., 1993; Werb, in the Str1 gene (StrlϪ/Ϫ) were made by homologous recombination us- 1997), and can autoactivate pro-Str1 and other pro-MMPs ing the AB2.1 ES cell line from 129 mice (Mudgett et al., 1998), and were to initiate a proteolytic cascade (Nagase, 1997). It is syn- compared with a control line (Str1ϩ/ϩ) on the 129 background. These mice were also grossly normal. To standardize lactation from mouse to thesized and secreted by a subpopulation of stromal cells mouse, litters were adjusted to six pups per dam, and mothers were in mammary gland (Witty et al., 1995). Targets for protein- housed individually before weaning. For time points during pregnancy, 0.5 ase activity are not limited to extracellular matrix (ECM) days post coitum (dpc) is assumed to be noon of the day of observation of molecules. Cell surface molecules such as E-cadherin can the vaginal plug. Lactation is timed from the time of parturition. be cleaved in cultured mammary epithelial cells trans- fected with an inducible Str1 cDNA (Lochter et al., 1997; Histology and Immunochemistry Werb, 1997; Sternlicht and Werb 2000). Other substrates For histologic evaluation, pieces of mammary gland were fixed in 4% include extracellular growth factors and cell-surface mole- paraformaldehyde overnight at 4ЊC, embedded in paraffin, sectioned and stained with hematoxylin and eosin (H&E) according to standard tech- cules (Werb, 1997). niques. For immunostaining of specific ECM molecules, 5 – 10 mm pieces To test the importance of MMPs in involution in the of fresh mammary gland were infiltrated with 20% sucrose in 1 mM present study, we have used two genetic approaches. We EDTA, 50 mM Tris pH 7.5 (4ЊC) and frozen in OCT for cryosectioning. have investigated mammary gland involution in mice over- Sections (6–10 ␮m) were cut and immediately fixed in 4% freshly pre- expressing the tissue inhibitor of matrix metalloprotein- pared paraformaldehyde for 15 min, blocked in 0.1 M glycine (3 ϫ 1 min in PBS), and then 10% sheep serum in PBS for 30 min at room tempera- ases, human TIMP-1 (TO) (Alexander et al., 1996), and in ture. Anti–entactin antibody (diluted 1:1,000 in 3% bovine serum albumin mice carrying a null mutation in Str1 (Str1Ϫ/Ϫ) (Mudgett in Tris-buffered saline) was incubated on sections overnight at 4ЊC, et al., 1998). Both of these transgenic mice have no overt washed three times in PBS/0.1% Tween for 5 min, and incubated with sec- defects and are able to complete pregnancy and lactate. ondary antibody (HRP-conjugated anti–rat IgG, diluted 1:100 into 20% Carnation skim milk powder in PBS) for 60 min. The wash protocol was Analysis of mammary glands from TO mice shows that the repeated and the sections were counterstained lightly with methylene transgene is expressed and active (Alexander et al., 1996). blue. By combining the information from these two strains, we can identify processes that require Str1 activity (if both Gel Electrophoresis of Mammary Gland Protein Lysates TO and Str1Ϫ/Ϫ transgenic mice share the same pheno- Pieces of mammary gland tissue were homogenized in RIPA buffer (150 type) and those that require TIMP-1–inhibitable MMP ac- mM NaCl, 1% NP-40, 0.5% deoxycholate, 0.1% SDS, 50 mM Tris-HCl, tivity (if TO but not Str1Ϫ/Ϫ mice show a specific pheno- pH 8.0) at 0.25 mg wet weight/ml. Lysates were spun for 15 min at 4ЊC in a type). We show here that a Str1 deficiency specifically microcentrifuge, and insoluble fractions (ECM-enriched fractions) were accelerates the differentiation of adipocytes during active washed once in RIPA buffer and boiled into sample buffer containing 5% SDS as described previously (Alexander et al., 1996). Extracts equivalent remodeling, and that epithelial cell death is unaffected in to 8 mg wet weight tissue were separated on 6% SDS-PAGE gels, and ei- either transgenic strain. ther stained with Coomassie blue or silver stain, or transferred to Immo- bilon P for immunoblotting of specific ECM constituents. Materials and Methods Assay of Apoptotic DNA Laddering mg) were digested in lysis buffer (0.2 100ف) Materials Fragments of mammary tissue mg/ml proteinase K in 50 mM Tris-HCl, 0.1 M NaCl, 0.1 M EDTA, 1% Ultraspec RNA isolation solution was from Biotecx.
Load more

Recommended publications
  • WMIC 2015 Plenary Speaker Zena Werb, Ph.D., Professor University Of
    WMIC 2015 Plenary Speaker Zena Werb, Ph.D., Professor University of California, San Francisco San Francisco, California, USA, Focus of WMIC 2015 Plenary Talk: Intravital Imaging Reveals Properties of Cancer Progression, Mestastasis and Response to Therapy Zena Werb, Ph.D. Dr. Zena Werb received her B.Sc. in Biochemistry from the University of Toronto, and her Ph.D. in Cell Biology from Rockefeller University, New York. After postdoctoral studies at the Strangeways Research Laboratory in Cambridge England, she was recruited to the faculty of the University of California, San Francisco, where she is currently Professor and Vice‐Chair of Anatomy. Her honors include the Charlotte Friend Award of the American Association for Cancer Research, the Alexander von Humboldt Research Award and the Colin Thomson Memorial Medal from the Association for International Cancer Research. Dr. Werb has been elected to the National Academy of Sciences, the Institute of Medicine, and the American Academy of Arts and Sciences. She has published more than 400 papers. Dr. Werb is recognized internationally for her fundamental discoveries about the molecular and cellular bases of extracellular matrix proteolysis by matrix metalloproteinases and their roles in the normal functioning and pathogenesis of tissues. Her studies have led to new paradigms about the role of the cellular microenvironment and intercellular communication in breast development and breast cancer. Her current research uses mouse models of breast cancer and patient‐derived breast cancer xenografts to study normal mammary development and its perturbation during tumor progression and metastasis. .
    [Show full text]
  • An Interview with Zena Werb
    Disease Models & Mechanisms 3, 513-516 (2010) doi:10.1242/dmm.006338 © 2010. Published by The Company of Biologists Ltd A MODEL FOR LIFE The extracellular matrix and disease: an interview with Zena Werb Zena Werb’s pioneering efforts brought recognition to the idea that the extracellular matrix has a profound influence in determining cell fate. Here, she discusses how a ‘rocky’ start in geophysics led her to a career that is changing the way we think about cancer. I started college. Ironically, earthquakes veryone is influenced by what became an important part of my life as a goes on around them, and cells resident of San Francisco, but I didn’t realise are much the same. The signalling this would be the case then. Back in college, Emolecules and support structures I wanted to go on a summer geology field of the extracellular matrix (ECM) course to the Rockies. I was one of the top direct many aspects of normal cell two students in my class, but they wouldn’t behaviour, including shape, migration and let me go because I was female – they said survival. However, the ECM can also play that there were not the proper facilities on a role in the development and progression the site for women. Instead, I found a DMM of disease. For example, a cell does not summer job in the field and actually got become cancerous on its own – together paid for the experience I gained, which with intrinsic changes, oncogenesis is would not have happened if I’d been encouraged by cues from the surrounding allowed into the course.
    [Show full text]
  • Extracellular Matrix Degradation and Remodeling in Development and Disease
    Downloaded from http://cshperspectives.cshlp.org/ on September 30, 2021 - Published by Cold Spring Harbor Laboratory Press Extracellular Matrix Degradation and Remodeling in Development and Disease Pengfei Lu1,2, Ken Takai2, Valerie M. Weaver3, and Zena Werb2 1Breakthrough Breast Cancer Research Unit, Paterson Institute for Cancer Research and Wellcome Trust Centre for Cell Matrix Research, Faculty of Life Sciences, University of Manchester, Manchester M20 4BX, United Kingdom 2Department of Anatomy and Program in Developmental Biology, University of California, San Francisco, California 94143-0452 3Department of Surgery and Center for Bioengineering and Tissue Regeneration, University of California, San Francisco, California 94143 Correspondence: [email protected] The extracellular matrix (ECM) serves diverse functions and is a major component of the cellular microenvironment. The ECM is a highly dynamic structure, constantly undergoing a remodeling process where ECM components are deposited, degraded, or otherwise modified. ECM dynamics are indispensible during restructuring of tissue architecture. ECM remodeling is an important mechanism whereby cell differentiation can be regulated, including processes such as the establishment and maintenance of stem cell niches, branch- ing morphogenesis, angiogenesis, bone remodeling, and wound repair. In contrast, abnor- mal ECM dynamics lead to deregulated cell proliferation and invasion, failure of cell death, and loss of cell differentiation, resulting in congenital defects and pathological processes including tissue fibrosis and cancer. Understanding the mechanisms of ECM remodeling and its regulation, therefore, is essential for developing new therapeutic inter- ventions for diseases and novel strategies for tissue engineering and regenerative medicine. he extracellular matrix (ECM) forms a milieu versatile and performs many functions in addi- Tsurrounding cells that reciprocally influ- tion to its structural role.
    [Show full text]
  • Testimony of Paul Berg, Ph.D. Chair, Public Policy Committee The
    THE AMERICAN SOCIETY FOR OFFICERS SUZANNE PFEFFER CELL President BIOLOGY HARVEY LODISH President-Elect GARY BORISY NATIONAT. OFFICE: 8120 Woodmont Avenue, Suite 750 Bethesda, Maryland 20814-2762 Past-President TEL: 301/347-9300 FAX: 301/347-9310 E-MAIL: [email protected] www.ascb.org LAWRENCE S. B. GOLDSTEIN Secretary GARY WARD Treasurer ELIZABETH MARINCOLA Testimony of Executive Director COUNCIL HELEN BLAU Paul Berg, Ph.D. ANTHONY BRETSCHER KEVIN P. CAMPBELL Chair, Public Policy Committee PIETRO DE CAMILLI ALAN RICK HORWITZ The American Society KATHRYN E, HOWELL for Cell Biology SANDRA L. SCHMID JEAN SCHWARZBAUER W. SUE SHAFER JANET SHAW to the JULIE THERIOT PETER WALTER COMMITTEE CHAIRS Senate Judiciary Committee DON CLEVELAND Constitution & By-Laws KENNETH R. MILLER Education United States Senate GARY WARD Finance ENRIQUE RODRIGUEZ-BOULAN International Affairs MATTHEW WELCH Local Arrangements LAWRENCE S. B. GOLDSTEIN March 19, 2003 Mentbership DONELLA J. WILSON Minorities Affairs RICHARD HYNES Nominating KATHERINE L. WILSON Public Information PAUL BERG Public Policy VIVEK MALHOTRA Scientific Meetings ZENA WERB Women in Cell Biology CELL BIOLOGY EDUCATION A, MALCOLM CAMPBELL Co-Editor-in-Chief SARAH C. R. ELGIN Co-Editor-in-Chief MOLECULAR BIOLOGY OF THE CELL KEITH R. YAMAMOTO Editor-in-Chief Statement of Paul Berg Robert and Vivian Cahill Professor, Emeritus of Cancer Research and Biochemistry Director, Emeritus of the Beckman Center for Molecular and Genetic Medicine, Stanford University Medical Center Chair, Public Policy Committee, The American Society for Cell Biology Mr. Chairman, Members of the Committee, thank you for inviting me to testify on this most important issue. I have followed the debate on the cloning questions we will address today and | welcome the opportunity to submit my own views on the matter.
    [Show full text]
  • Metastasis and Invasion 3 – Metastasis Science Cancer
    CANCER SCIENCE 3 Cancer Science 3 – Metastasis and Invasion 3 – Metastasis Science Cancer www.ipsen.com 2FI 0069 Metastasis and Invasion Tuscany, May 20-23, 2007 24, rue Erlanger – 75016 Paris – Tel.: 33(0)1 44 96 10 10 – Fax: 33(0)1 44 96 11 99 COLLOQUES MÉDECINE ET RECHERCHE Fondation Ipsen SCIENTIFIC REPORT BY APOORVA MANDAVILLI 2 Fondation Ipsen is placed under the auspices of Fondation de France MOLECULAR MARKERS 3 4 Foreword by Inder M. Verma 7 Part I: Molecular markers 9 J. Michael Bishop Senescence and metastasis in mouse models of breast cancer 15 Joan Massagué Metastasis genes and functions 21 Zena Werb Transcriptional regulation of the metastatic program 25 Inder M. Verma BRCA1 maintains constitutive heterochromatin formation: a unifying hypothesis of its function 29 Tak Wah Mak The role of RhoC in development and metastasis 35 Part II: Motility and invasiveness 37 Robert Weinberg Mechanisms of malignant progression 43 Daniel Louvard Fascin, a novel target of b-catenin-Tcf signaling, is expressed at the invasive front of human colon cancer 49 Gerhard Christofori Distinct mechanisms of tumor cell invasion and metastasis 55 Douglas Hanahan Multiple parameters influence acquisition by solid tumors CONTENTS of a capability for invasive growth 59 Part III : Mechanisms of metastasis 61 Richard Hynes Cellular mechanisms contributing to metastasis 67 Ann Chambers Novel imaging approaches for studying tumor metastasis 73 Jeffrey Pollard Macrophages are a cellular toolbox that tumors sequester to promote their progression to malignancy 79 Wolf-Hervé Fridman T effector/memory cells, the ultimate control of metastasis in humans 85 Kari Alitalo Inhibition of lymphangiogenesis and metastasis 91 Shahin Rafii Contribution of CXCR4+VEGFR1+ pro-angiogenic hematopoietic cells to tumor oncogenesis 97 Part IV : Cancer stem cells 99 Paolo Comoglio Invasive growth : a MET-driven genetic program for cancer and stem cells 105 Hans Clevers Wnt and Notch cooperate to maintain proliferative compartments in crypts and intestinal neoplasia 111 Owen N.
    [Show full text]
  • Conference Program
    Conference Program Note: All Scientific Sessions will be held in the Omni Hotel at 675 L Street. Poster Sessions will be held at the Hard Rock Hotel at the corner of 5th Avenue & L Street. Sunday, January 20 7:00 p.m.-7:10 p.m. Welcoming Remarks 7:10 p.m.-8:00 p.m. Keynote Address Omni Hotel San Diego, Grand Ballroom Metastasis and diversity in breast cancer Kornelia Polyak, Dana-Farber Cancer Institute, Boston, MA 8:00 p.m.-9:30 p.m. Opening Reception Monday, January 21 7:00 a.m.-8:00 a.m. Continental Breakfast Omni Hotel San Diego, Art Gallery 8:00 a.m.-10:00 a.m. Session 1: The Soil Session Chairperson: Zena Werb, Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, CA Omni Hotel San Diego, Grand Ballroom Microenvironmental control of bone metastasis Sylvain Provot, INSERM, Paris, France The role of the microenvironment protein cathelicidin LL-37 in pancreatic ductal adenocarcinoma* Christopher Heeschen, Spanish National Cancer Research Centre (CNIO), Madrid, Spain Normalizing tumor cell metabolism in breast cancer metastasis: A novel therapeutic approach Brunhilde Felding-Habermann, Scripps Research Institute, La Jolla, CA Identification of luminal breast cancers that establish a tumor supportive macroenvironment defined by proangiogenic platelets and bone marrow derived cells* Timothy Marsh, Brigham and Women’s Hospital, Boston, MA The extracellular matrix is fertile soil Richard Hynes, Massachusetts Institute of Technology, Cambridge, MA *Short talks from proffered papers Program and Proceedings • January 20-23, 2013 • San Diego, CA 7 Program 10:00 a.m.-10:30 a.m.
    [Show full text]
  • Meeting Report
    View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by Elsevier - Publisher Connector Cell Stem Cell Meeting Report Cancer and Stem Cell Biology: How Tightly Intertwined? Carla F. Kim1,2,3,* and Peter B. Dirks4,* 1Stem Cell Program, Children’s Hospital Boston, Boston, MA 02115, USA 2Department of Genetics, Harvard Medical School, Boston, MA 02115, USA 3Harvard Stem Cell Institute, Cambridge, MA 02138, USA 4Developmental and Stem Cell Biology Program, Department of Surgery, Arthur and Sonia Labatt Brain Tumor Research Center, Hospital for Sick Children, University of Toronto, 555 University Avenue, Toronto, Ontario M5G1X8, Canada *Correspondence: [email protected] (C.F.K.), [email protected] (P.B.D.) DOI 10.1016/j.stem.2008.07.012 Ever since the discovery of cancer stem cells in leukemia and, more recently, in solid tumors, enormous attention has been paid to the apparent stem cell nature of cancer. These concepts were the focus of the ‘‘Stem Cells and Cancer’’ symposium held recently at the University of California, San Francisco, and the inspiration for this overview of current research and important questions emerging in this area. This year’s annual UCSF Helen Diller Family Comprehensive confer these properties accumulate. When these additional Cancer Center Symposium focused on stem cells and cancer. events occur in progenitor cell populations derived from mutant This symposium provided a representation of all facets of stem HSC clones, cancer progression occurs. Thus, the phenotype of cell biology: from the role of stem and progenitor cells in devel- the cancer stem cell may be more similar to the normal progen- opment to adult tissues, normal stem cells versus cancer stem itor population than to the HSC itself.
    [Show full text]
  • Iman Aftab Khan
    MOLECULAR MECHANISMS OF ERBB2-DRIVEN THREE-DIMENSIONAL BREAST TUMOUR GROWTH. By Iman Aftab Khan Submitted in partial fulfilment of the requirements for the degree of Doctor of Philosophy At Dalhousie University Halifax, Nova Scotia August 2018 © Copyright by Iman Aftab Khan, 2018 Dedicated to my parents Late Dr. Aftab Ahmad Khan and Mrs. Fatima Bisquerra Khan For their unconditional love, patience and struggle to support my decisions that helped me realize my dreams. ii Table of Contents LIST OF TABLES ........................................................................................................... ix LIST OF FIGURES .......................................................................................................... x ABSTRACT .................................................................................................................... xiii LIST OF ABBREVIATIONS USED ............................................................................ xiv ACKNOWLEDGEMENTS ......................................................................................... xxv CHAPTER 1. INTRODUCTION .................................................................................... 1 Resistance to detachment-induced cell death as a critical feature of ErbB2- driven breast cancer: an overview of project goals. ...................................................... 1 1.1 The role of the cell-ECM interactions in the mammary gland development and functions..................................................................................
    [Show full text]
  • Suffrage Science Contents
    Suffrage science Contents Introduction Brenda Maddox and Vivienne Parry on sex and success in science 3 Love Professor Sarah-Jayne Blakemore and Dr Helen Fisher on love and social cognition 6 Life Professor Liz Robertson and Dr Sohaila Rastan on developmental biology and genetics 10 Structure Professor Dame Louise Johnson and Professor Janet Thornton on structural biology 15 Strife Professors Fiona Watt and Mary Collins on cancer and AIDS 19 Suffrage Heirloom Jewellery Designs to commemorate women in science 23 Suffrage Textiles Ribbons referencing the suffrage movement 33 Index of Featured Women Scientists Pioneering female contributions to Life Science 43 Acknowledgements Contributions and partnerships 47 Tracing Suffrage Heirlooms Follow the provenance of 13 pieces of Suffrage Heirloom Jewellery 48 1 A successful career in science is always demanding of intellect “ hard work and resilience; only more so for most women. ” Professor Dame Sally C Davies From top, left to right: (Row 1) Anne McLaren, Barbara McClintock, Beatrice Hahn, Mina Bissell, Brenda Maddox, Dorothy Hodgkin, (Row 2) Brigid Hogan, Christiane Nüsslein-Volhard, Fiona Watt, Gail Martin, Helen Fisher, Françoise Barré-Sinoussi, (Row 3) Hilde Mangold, Jane Goodall, Elizabeth Blackburn, Janet Thornton, Carol Greider, Rosalind Franklin, (Row 4) Kathleen Lonsdale, Liz Robertson, Louise Johnson, Mary Lyon, Mary Collins, Vivienne Parry, (Row 5) Uta Frith, Amanda Fisher, Linda Buck, Sara-Jayne Blakemore, Sohaila Rastan, Zena Werb 2 Introduction To commemorate 100 years of International Women’s Day in 2011, Suffrage Science unites the voices of leading female life scientists Brona McVittie talks to Vivienne Parry and Brenda Maddox about sex and success in science Dorothy Hodgkin remains the only British woman to Brenda Maddox is author of The Dark Lady of DNA, have been awarded a Nobel Prize for science.
    [Show full text]
  • The Extracellular Matrix Ligands Fibronectin
    Molecular Biology of the Cell Vol. 5, 439-453, April 1994 The Extracellular Matrix Ligands Fibronectin and Tenascin Collaborate in Regulating Collagenase Gene Expression in Fibroblasts Patrice Tremble,* Ruth Chiquet-Ehrismann,t and Zena Werb* *Laboratory of Radiobiology and Environmental Health, University of California, San Francisco, California 94143-0750; and tFriedrich Meischer Institute, CH-4002 Basel, Switzerland Submitted June 14, 1993; Accepted February 14, 1994 Monitoring Editor: Richard Hynes Tenascin (TN) is a large oligomeric glycoprotein that is present transiently in the extracellular matrix (ECM) of cells and is involved in morphogenetic movements, tissue patterning, and tissue repair. It has multiple domains, both adhesive and anti-adhesive, that interact with cells and with fibronectin (FN) and other ECM macromolecules. We have studied the consequences of the interaction of TN with a FN matrix on gene expression in rabbit synovial fibroblasts. Fibroblasts plated on a mixed substrate of FN and TN, but not on FN alone, upregulated synthesis of four genes: collagenase, stromelysin, the 92-kDa gelatinase, and c-fos. Although the fibroblasts spread well on both FN and FN/TN substrates, nuclear c-Fos increased within 1 h only in cells that were plated on FN/TN. TN did not induce the expression of collagenase in cells plated on substrates of type I collagen or vitronectin (VN). Moreover, soluble TN added to cells adhering to a FN substrate or to serum proteins had no effect, suggesting that TN has an effect only in the context of mixed substrates of FN and TN. Collagenase increased within 4 h of plating on a FN/TN substrate and exhibited kinetics similar to those for induction of collagenase gene expression by signaling through the integrin FN receptor.
    [Show full text]
  • IN THIS ISSUE Top-Rated Status! Involved in the Division of Specific Cancer Types
    Thirtieth Anniversary Edition // SPRING 2015 Cancer Throughout the Years John Kemshead, PhD Bruce Chabner, MD Chairmen, Scientific Advisory Board Scientific Advisory Board, Emeritus The time my colleagues have spent with the Foundation was The Foundation has been in existence for 30 years and transformative. Beginning in the late 1980's, we had the belief that how have things changed during this time? On multiple the treatment of cancer would be completely changed and placed occasions you read in the news about breakthroughs in on a more rational footing by rapidly expanding knowledge of the treatment but have these really turned into a reality? genetics causing cancer. A particular meeting in the late 1980's which had the participation of many of the leading scientists and clinical researchers in the field Thirty years ago cancer treatment focused upon the was the key event. The idea was presented that the genetic changes underlying mainstays of surgery, radiation therapy and the various kinds of cancer would become the targets for new therapies, "targeted chemotherapy. In addition, diagnosis relied primarily therapies". That has proven to be true, and the concept has led to the expansion upon CT scans, X-rays and the skills of both the of the field of "precision medicine" recently endorsed by the President in his State pathologist and oncologist. Through the development of of Union speech. Many of the subsequent sessions of the Foundation dealt with the Magnetic Resonance Imaging (MRI) scanner, aspects of this larger change. There is no doubt that this concept has radically Positron Emission Tomography (PET) scans, monoclonal altered and improved cancer treatment, and given us real hope that the disease antibodies and the Polymerase Chain Reaction (PCR) can be effectively treated if we only understand its causes.
    [Show full text]
  • Zena Werb 1945–2020
    obituary Zena Werb 1945–2020 nlike 30 years ago, when the notion of tumor cells being regulated by Ucell-extrinsic mechanisms was akin to heresy, the tumor microenvironment (TME) is now recognized as a hallmark of cancer, with a broad community of researchers focusing on how it regulates malignant transformation, metastasis and therapy response. We owe this evolution in thinking to several scientific giants, but perhaps none more impactful in changing the storyline than Zena Werb, our intellectually fearless colleague, beloved mentor and generous friend, who died suddenly on 16 June 2020 at the age of 75. Zena was a professor and vice chair in the Department of Anatomy at the University of California San Francisco (UCSF) for over 40 years and was the associate director for basic science at the UCSF Helen Diller Family Comprehensive Cancer Center. Her foundational work on macrophage physiology, the extracellular matrix (ECM), mammary gland development, breast cancer and tumor-associated inflammation made Zena Werb as a graduate student at Rockefeller University, circa 1971. Credit: Rockefeller Grad – News her one of the most respected researchers and Notes. June 1971 Vol 2. No 10. in the world. Zena’s contributions led to numerous awards and honors, including election to the National Academy of John T. Dingle at the Strangeways Research that Zena forged an enduring collaboration Sciences and the American Association Laboratory, in Cambridge, England, she with Mina J. Bissell, who introduced her to for Cancer Research, presidency of the began investigating a new (at the time) mammary gland development and cancer. American Society of Cell Biology, the E.B.
    [Show full text]