DOCSLIB.ORG

Changes in Expression of Putative Antigens Encoded by Pigment

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Changes in Expression of Putative Antigens Encoded by Pigment Proc. Natl. Acad. Sci. USA Vol. 92, pp. 10152-10156, October 1995 Medical Sciences Changes in expression of putative antigens encoded by pigment genes in mouse melanomas at different stages of malignant progression (albino locus/brown locus/slaty locus/silver locus) SETH J. ORLOW*, VINCENT J. HEARINGt, CHIE SAKAIt, KAZUNORI URABEt, BAO-KANG ZHOU*, WILLYS K. SILVERSt, AND BEATRICE MINTZO§ *Ronald 0. Perelman Department of Dermatology and Department of Cell Biology, New York University School of Medicine, New York, NY 10016; tLaboratory of Cell Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892; and tInstitute for Cancer Research, Fox Chase Cancer Center, Philadelphia, PA 19111 Contributed by Beatrice Mintz, July 25, 1995 ABSTRACT Cutaneous melanomas of Tyr-SV40E trans- This problem might be overcome by identifying changes in genic mice (mice whose transgene consists of the tyrosinase the antigenic profile associated with melanoma progression promotor fused to the coding regions of simian virus 40 early such that the design of a treatment protocol could encompass genes) strikingly resemble human melanomas in their devel- all the melanoma cells. Such a characterization in the case of opment and progression. Unlike human melanomas, the human melanoma would be complicated by genetic differences mouse tumors all arise in genetically identical individuals, among individuals, especially as the genetic background, as thereby better enabling expression of specific genes to be well as allelic differences at pigment gene loci themselves, can characterized in relation to advancing malignancy. The prod- influence the expression and interactions of these genes (11, ucts of pigment genes are of particular interest because 12). The melanomas of Tyr-SV40E transgenic mice [mice peptides derived from these proteins have been reported to whose transgene consists of the tyrosinase promoter fused to function as autoantigens with immunotherapeutic potential in the coding regions of simian virus 40 (SV40) early genes], on some melanoma patients. However, the diminished pigmen- the other hand, afford an opportunity to investigate the tation characteristic of advanced melanomas raises the products of pigment genes in tumors arising in genetically many identical (C57BL/6 inbred strain) animals and representing all possibility that some of the relevant products may no longer stages of tumor progression (13-16). Unlike long-established be expressed in the most malignant cells. We have therefore cell culture lines of animal or human melanomas that have investigated the contributions of several pigment genes in been experimentally selected for a particular pigmentary or melanotic vs. relatively amelanotic components of primary other phenotype, the phenotypes of the transgenic mouse and metastatic mouse melanomas. The analyses reveal melanomas reflect the progression actually taking place in marked differences within and among tumors in levels of vivo. mRNAs and proteins encoded by the wild-type alleles at the The Tyr-SV40E transgene confers melanoma susceptibility albino, brown, slaty, and silver loci. Tyrosinase (the protein by activation of SV40 transforming sequences under the encoded by the albino locus) was most often either absent or transcriptional control of the mouse tyrosinase promoter, undetectable as melanization declined. The protein encoded which is encoded at the albino locus and is specifically ex- by the slaty locus (tyrosinase-related protein 2) was the only pressed in pigment cells (13). The transgene acts as an one of those tested that was clearly present in all the tumor initiating stimulus in melanocytes, only rarely giving rise samples. These results suggest that sole reliance on targeting spontaneously to cutaneous melanomas. If the cells are further tyrosinase-based antigens might selectively favor survival of subjected to growth-promoting influences in vitro (17, 18) or more malignant cells, whereas targeting the ensemble of the in vivo (19), they may become tumorigenic. Cutaneous mela- antigens tested might contribute toward a more inclusive and nomas are experimentally inducible by taking advantage of the effective antimelanoma strategy. existence of separate transgenic lines of mice, each descended from a single egg injected with transgene DNA and having a Immunotherapy based on recognition by cytotoxic T lympho- characteristic level of transgene expression (13). By grafting cytes of antigenic peptides on melanoma cells has shown skin from mice of a line with high expression, and therefore promise in the treatment of cutaneous melanoma (1-9). high melanoma susceptibility, to hosts of a low-susceptibility Among the melanoma antigens thus far identified are proteins line, the donor skin may be exposed to growth factors and or encoded genes cytokines associated with wound healing. Melanomas fre- peptides by specific pigment genes-i.e., quently develop in the grafts and metastasize in the hosts (15), involved in melanin production. A major problem is that whose risk of eye melanomas, especially in the retinal pigment melanomas tend to become amelanotic as the malignancy epithelium (20), is far below that of the donors. The his- progresses, and can therefore be expected to lose expression of topathogenesis of these mouse skin melanomas (16) strikingly some of these genes. The gradual emergence of increasing resembles that of human cutaneous melanomas (21). numbers of hypomelanotic or amelanotic cells in the primary We examine the expression in the mouse melanomas of four tumors or their metastases increases the possibility that such pigment genes whose protein homologues have been impli- cells will selectively escape immune destruction. The superior cated as autoantigens in human melanoma. The products of all mitotic activity of the amelanotic cells (10) may in fact four genes become localized in melanosomes, the organelles in exacerbate the course of the disease after the tumor burden which melanin is synthesized. Three of them are known to has been temporarily reduced by the death of melanotic cells. catalyze steps in melanin biosynthesis: they are tyrosinase (EC The publication costs of this article were defrayed in part by page charge Abbreviations: SV40, simian virus 40; TRP-1 and -2, tyrosinase- payment. This article must therefore be hereby marked "advertisement" in related protein 1 and 2, respectively. accordance with 18 U.S.C. §1734 solely to indicate this fact. §To whom reprint requests should be addressed. 10152 Downloaded by guest on September 27, 2021 Medical Sciences: Orlow et al. Proc. Natl. Acad. Sci. USA 92 (1995) 10153 1.14.18.1), the rate-limiting enzyme and the product of the bridized with other probes as necessary. TYRS-J, a probe mouse albino locus (22-24); tyrosinase-related protein 1 specific for tyrosinase, was kindly provided by H. Yamamoto (TRP-1), which functions as 5,6-dihydroxyindole-2-carboxylic and T. Takeuchi (Sendai, Japan); pMT4, which is specific for acid oxidase and is encoded at the mouse brown locus (25); and TRP-1, was provided by S. Shibahara (Sendai, Japan); and tyrosinase-related protein 2 (TRP-2), which has 3,4-dihy- TRP-2a, which is specific for TRP-2, was a gift from I. Jackson droxyphenylalanine (DOPA)chrome tautomerase (EC (Edinburgh). 5.3.3.12) function and is encoded at the mouse slaty locus (26, Melanogenic Assays. Tissues were homogenized in 1% 27). The fourth gene product, initially designated Pmel 17, is Nonidet P-40/0.01% SDS/0.1 M Tris-HCl, pH 7.2/1 ,ug of the product of the silver locus and is incorporated into the aprotinin per ml/100 ,tM phenylmethylsulfonyl fluoride on ice melanosomal matrix (28, 29); its enzymatic function, if any, by using a Potter-Elvehjem glass homogenizer, incubated for remains unknown. Comparisons of melanotic and relatively 1 h at 4°C, and then stored at -70°C until used. Following amelanotic components of the mouse melanomas analyzed centrifugation at 12,000 x g for 3 min, the supernatants were here reveal marked disparities within and among tumors, used for melanogenic assays. Four assays for melanogenic including cases of absent or borderline expression of some of catalytic activities, as described below, were carried out at pH the proteins. The exception was TRP-2, which was found in all 6.8 and 37°C for 60 min. the tumor examples analyzed. (i) Tyrosine hydroxylase activity was measured by using the [3H]tyrosine assay (31, 32). This method specifically measures the tritiated water produced during the hydroxylation of MATERIALS AND METHODS tyrosine to DOPA. (ii) DOPA oxidase activity was measured Melanomas. The melanomas in this study all arose in skin on the basis of incorporation of [3-14C]DOPA into acid- from Tyr-SV40E hemizygous donors of line 8, which are highly insoluble melanin, as described (30). (iii) DOPAchrome tau- susceptible to melanoma, after discs of skin were grafted to tomerase activity was measured by HPLC (33, 34) as the low-susceptibility hemizygous hosts of line 12 (15). Four disappearance of DOPAchrome substrate and the production primary melanomas (designated P) and two metastases (des- of 5,6-dihydroxyindole-2-carboxylic acid rather than 5,6- ignated M) were analyzed. These primary melanomas were dihydroxyindole; data were converted to pmol of products by chosen because they were zonal tumors in which a deeply comparison with known standards. (iv) Melanin production melanotic and an apparently amelanotic zone were clearly was measured by incorporation of [14C]tyrosine into acid- evident
Load more

Recommended publications
  • Beatrice Mintz Date of Birth 24 January 1921 Place New York, NY (USA) Nomination 9 June 1986 Field Genetics Title Jack Schultz Chair in Basic Science
    Beatrice Mintz Date of Birth 24 January 1921 Place New York, NY (USA) Nomination 9 June 1986 Field Genetics Title Jack Schultz Chair in Basic Science Professional address The Institute for Cancer Research Fox Chase Cancer Center 7701 Burholme Avenue, Room 215 Philadelphia, PA 19111 (USA) Most important awards, prizes and academies Awards: Bertner Foundation Award in Fundamental Cancer Research (1977); New York Academy of Sciences Award in Biological and Medical Sciences (1979); Papanicolaou Award for Scientific Achievement (1979); Lewis S. Rosenstiel Award in Basic Medical Research (1980); Genetics Society of America Medal (1981); Ernst Jung Gold Medal for Medicine (1990); John Scott Award for Scientific Achievement (1994); March of Dimes Prize in Developmental Biology (1996); American Cancer Society National Medal of Honor for Basic Research (1997); Pearl Meister Greengard Prize (2008); Albert Szent-Györgyi Prize for Progress in Cancer Research (2011). Academies: National Academy of Sciences (1973); Fellow, American Association for the Advancement of Science (1976); Honorary Fellow, American Gynecological and Obstetrical Society (1980); American Philosophical Society (1982); Fellow, American Academy of Arts and Sciences (1982); Pontifical Academy of Sciences (1986). Degrees: Doctor of Science, New York Medical College (1980); Medical College of Pennsylvania (1980); Northwestern University (1982); Hunter College (1986); Doctor of Humane Letters, Holy Family College (1988). Summary of scientific research Beatrice Mintz discovered the underlying relationship between development and cancer. She first showed that development is based on an orderly hierarchical succession of increasingly specialized small groups of precursor or "stem" cells, expanding clonally. She proposed that cancer involves a regulatory aberration in this process, especially in the balance between proliferation and differentiation.
    [Show full text]
  • From Blastomeres to Somatic Cells: Reflections on Cell Developmental Potential in Light of Chimaera Studies – a Review
    Animal Science Papers and Reports vol. 35 (2017) no. 3, 225-240 Institute of Genetics and Animal Breeding, Jastrzębiec, Poland From blastomeres to somatic cells: reflections on cell developmental potential in light of chimaera studies – a review Krystyna Żyżyńska-Galeńska*, Anna Piliszek, Jacek A. Modliński Department of Experimental Embryology, Institute of Genetics and Animal Breeding, Polish Academy of Sciences, Jastrzębiec, 05-551 Magdalenka, Poland (Accepted June 10, 2017) Mammalian development is a process, whereby cells from a totipotent zygote gradually lose their potency, i.e. their ability to differentiate, in the environment of the developing embryo. An ideal model for testing the real potential of cells is the experimental production of chimaeras. The first experimentally produced mammalian (murine) chimaeras were created by Tarkowski [1961] and since then many new methods of chimaera production have been developed, including injecting cells into the blastocyst’s cavity or into cleaving embryos. This review describes how different cell types, depending on the developmental stage or culture conditions, manifest their potential to contribute to chimaeras. Cell developmental potential has been analysed in pluripotent blastomeres, which can contribute to all embryonic and extra-embryonic lineages, albeit differently depending on their developmental stage. This is the case in blastocyst lineages, with various developmental potentials depending on the surrounding cells, and in more differentiated cells from different stages of pregnancy, which in some cases may colonise chimaeric animal tissue. Cell potential has also been analysed in embryonic stem and embryonal carcinoma cells, which are pluripotent and efficiently contribute to chimaeras; in multipotent fetal and adult stem cells, which can also participate in chimaera formation; and in somatic mouse embryonic fibroblasts (MEFs), which can also be reprogrammed in the environment of the cleaving embryo.
    [Show full text]
  • Blanche Capel, Phd FASEB Board of Directors
    Blanche Capel, PhD FASEB Board of Directors Blanche Capel, PhD, is a James B. Duke Professor of Cell Biology at Duke University Medical Center, where she began her research laboratory in 1993. Her graduate training was in mouse genetics and stem cell biology with Beatrice Mintz at Fox Chase Cancer Center and the University of Pennsylvania, followed by postdoctoral research in the Lovell-Badge laboratory at the National Institute for Medical Research, Mill Hill, London, leading to the discovery of Sry, the male sex determining gene in mammals. Work from the Capel laboratory is prominent in the field of primary sex determination and the cell fate and patterning decisions that underlie the development of the early bipotential mammalian gonad into either testis or ovary. Dr. Capel’s work on signaling pathways in the gonad led to the widely accepted current model that sex determination results from antagonism between the male and female transcriptional and cell signaling networks. She pioneered organ culture techniques for studying the organogenesis of the testis and ovary, and was among the first to develop live imaging to explore the critical role of the vasculature in the morphogenesis of the gonad. Recently, she has used systems-biology and mouse genetics approaches to characterize the global transcriptional network underlying gonad fate, and has investigated the conservation of these mechanisms in the red-eared slider turtle, in which sex determination is thermally regulated. Other work in her laboratory aims to understand how the intracellular program in germ cells, in combination with regulation from their niche, leads to the transition of germ cells from a pluripotent state into pro-spermatogonia.
    [Show full text]
  • Rudolf Jaenisch
    RUDOLF JAENISCH Date of Birth: April 22, 1942 Place of Birth: Wolfelsgrund, Germany Citizenship: United States Education: M.D. 1967, University of Munich, Germany Associations, Memberships and Honors: Member, National Academy of Sciences Member, National Institute of Medicine Member, International Society for Stem Cell Research Member, American Association for the Advancement of Science Member, German Academy of Natural Sciences Leopoldina Associate Member, European Molecular Biology Organization Editorial Board, Proceedings of the National Academy of Sciences, 2004- Editorial Board, Developmental Dynamics, 1992-2000 1996 Boehringer Mannheim Molecular Bioanalytics Prize 2001 First Peter Gruber Foundation Award in Genetics 2002 Robert Koch Prize for Excellence in Scientific Achievement 2003 Charles Rodolphe Brupracher Foundation Cancer Award 2006 Max Delbrück Medal for Molecular Medicine 2007 Vilcek Foundation Prize for Achievements of Prominent Immigrants 2008 Meira and Shaul G. Massry Prize 2009 James R. Killian Jr. Faculty Achievement Award 2009 Ernst Schering Prize 2010 Orden Pour le Mérite 2010 Kazemi Prize of the Royan Institute 2010 Order of Merit of the Federal Republic of Germany 2011 MGH Warren Triennial Prize 2011 Wolf Prize for Medicine 2011 United States National Medal of Science 2011 J. Allyn Taylor International Prize in Medicine 2012 ISSCR McEwen Award for Innovation 2012-Vice President, International Society for Stem Cell Research 2013 Franklin Institute Laureate Professional Experience: 9/68-1/70 Postdoctoral Fellow, Max Planck Institute for Biochemistry, Munich; replication and transcription of E. coli phages M13 and PhiX174. 2/70-2/72 Postdoctoral Fellow with Dr. Arnold Levine, Department of Biochemistry, Princeton University; Replication, transcription, and transformation with SV40 virus. 2/72-10/72 Visiting Fellow with Dr.
    [Show full text]
  • III IIHIIII USOO5550316A United States Patent (19) 11 Patent Number: 5,550,316 Mintz 45) Date of Patent: Aug
    III IIHIIII USOO5550316A United States Patent (19) 11 Patent Number: 5,550,316 Mintz 45) Date of Patent: Aug. 27, 1996 54) TRANSGENIC ANIMAL MODEL SYSTEM M Bradlet al. (1991) Proc Natl AcadSci, USA 88:164-168. FOR HUMAN CUTANEOUS MELANOMA K N Broadley et al (1989) Laboratory Investigation 61:571-575. 75) Inventor: Beatrice Mintz, Elkins Park, Pa. Hesketh (1995) The Oncogene Facts Book, pp. 32-42. (73) Assignee: Fox Chase Cancer Center, Strojek et al (1988) Genetic Engineering: Principles and Philadelphia, Pa. methods, 10:238. Loudon et al (1993) Clin Exp Pharmacol Physiol 20: 21 Appl. No.: 11,060 283-288. 22 Filed: Jan. 29, 1993 Primary Examiner-Jacqueline M. Stone Related U.S. Application Data Assistant Examiner-Bruce R. Campell Attorney, Agent, or Firm-Pennie & Edmonds 63 Continuation-in-part of Ser. No. 636,798, Jan. 2, 1991, abandoned. 57) ABSTRACT (51 Int. CI.' ................ C12N 15/00; A01K 67/00 52) U.S. Cl. ..................... 800/2; 800/DIG. 1; 435/172.3; The present invention relates to transgenic animal model 536/23.1; 536/23.72; 536/24.1; 424/9.2 systems for human cutaneous melanoma. It is based, at least Field of Search ................................... 800/2, DIG. 1; in part, on the discovery that, in susceptible transgenic mice, (58) accelerated formation of melanoma tumors occurred near 435/172.3; 536/23.1, 23.72, 24.1; 424/9 the wound borders of skin grafts carrying the Tyr-SV40E References Cited transgene, indicating that factors present during wound (56) healing facilitate the formation of cutaneous melanoma in PUBLICATIONS susceptible tissue.
    [Show full text]
  • Normal Genetically Mosaic Mice Produced from Malignant
    Proc. Nat. Acad. Sci. USA Vol. 72, No. 9, pp. 3585-589, September 1975 Cell Biology Normal genetically mosaic mice produced from malignant teratocarcinoma cells (embryonal carcinoma/teratoma/embryoid body core cells/blastocyst injection/allophenic mice) BEATRICE MINTZ AND KARL ILLMENSEE Institute for Cancer Research, Fox Chase, Philadelphia, Pennsylvania 19111 C6ntributed by Beatrice Mintz, June 26, 1975 ABSTRACT Malignant mouse teratocarcinoma (or em- The most rigorous test possible for developmental totipo- bryonal carcinoma) cells with a normal modal chromosome tency would be significant contributions of the carcinoma number were taken from the "cores" of embryoid bodies cells to the normal differentiation of virtually all tissues in a grown only in vivo as an ascites tumor for 8 years, and were mouse. For this to occur, the initially malignant cells would injected into blastocysts bearing many genetic markers, in order to test the developmental capacities, genetic constitu- presumably have to be brought into association with early tion, and reversibility of malignancy of the core cells. Ninety- embryo cells so that the latter could provide an organiza- three live normal pre- and postnatal animals were obtained. tional framework appropriate for normal development. The Of 14 thus far analyzed, three were cellular genetic mosaics experiment is analogous to production of allophenic mice with substantial contributions of tumor-derived cells in many (6). developmentally unrelated tissues, including some never The projected teratoma studies in this laboratory involve seen in the solid tumors that form in transplant hosts. The tissues functioned normally and synthesized their specific the use of mutagenized embryonal carcinoma cells for ex- products (e.g., immunoglobulins, adult hemoglobin, liver pro- perimental analyses of genetic regulatory systems in mam- teins) coded for by strain-type alleles at known loci.
    [Show full text]
  • Karl Oskar Illmensee (1939–) [1]
    Published on The Embryo Project Encyclopedia (https://embryo.asu.edu) Karl Oskar Illmensee (1939–) [1] By: Lancaster, Cheryl Karl Oskar Illmensee studied the cloning [2] and reproduction of fruit flies, mice, and humans [3] in the US and Europe during the twentieth and twenty-first centuries. Illmensee used nuclear transfer techniques (cloning [2]) to create early mouse [4] embryos from adult mouse [4] cells, a technique biologists used in later decades to help explain how embryonic cells function during development. In the early 1980s, Illmensee faced accusations of fraud when others were unable to replicate the results of his experiments with cloned mouse [4] embryos. Illmensee also worked with human embryos, investigating how embryos split to form identical twins. Illmensee was born in Lindau, Austria, in 1939. At the Ludwig Maximilians Universität in München, Germany, he studied chemistry and biology before beginning his PhD research in the Zoologisches Institut der Universität (University Department of Zoology), part of the Ludwig Maximilians Universität. Illmensee studied the developmental genetics of fruit flies. Two other researchers, Robert Briggs and Thomas King at the American Institute for Cancer Research [5] in Washington, USA, had cloned frogs in the 1950s. Illmensee attempted to use Briggs and King's method to clone fruit fliesD (rosophila melanogaster [6]). Despite failing to clone an adult fly, Illmensee published the results of his research in 1968. Illmensee exchanged the nucleus [7] of an unfertilized fly egg [8] with a nucleus [7] from a fertilized fly egg [8], a process called nuclear transplantation. Of the 118 eggs that had undergone nuclear transplantation, 11 began to develop, and one developed into the larval stage, the stage right before adulthood in fruit flies.
    [Show full text]
  • History of The
    HISTORY OF THE AMERICAN GYNECOLOGICAL SOCIETY 1876-1981 AND AMERICAN ASSOCIATION OF OBSTETRICIANS AND GYNECOLOGISTS 1888-1981 EDWARD STEWART TAYLOR Denver, Colorado The C. V. Mosby Company ST. LOUIS, MISSOURI 1985 Copyright © 1985 by The C. V. Mosby Company All rights reserved. No part of this publication may be reproduced, stored in a retrieval system, or trans- mitted, in any form or by any means, electronic, mechanical, photocopying, recording, or otherwise, without written permission from the publisher. Printed in the United States of America The C. V. Mosby Company 11830 Westline Industrial Drive, St. Louis, Missouri 63146 Library of Congress Cataloging in Publication Data Taylor, E. Stewart (Edward Stewart), 1911- History of the American Gynecological Society, 1876- 1981, and the American Associate of Obstetricians and Gynecologists, 1888-1981. Includes index. 1. American Gynecological Society—History. 2. American Association of Obstetricians and Gynecologists—History. I. American Gynecological Society. II. American Association of Obstetricians and Gynecologists. III. Title. [DNLM: Gynecology—history—United States. 2. Obstetrics— history—United States. 3. Societies, Medical—history— United States, WP 1 A512T] RG1.A567T39 1985 618'.06’073 85-4768 ISBN 0-8016-5101-8 GW/OB/RR 9 8 7 6 5 4 3 2 1 01/C/088 Contents Preface. ......................................................................................................................................................... 5 Introduction. ................................................................................................................................................
    [Show full text]
  • March of Dimes Prize in Developmental Biology Recipient List
    MARCH OF DIMES PRIZE IN DEVELOPMENTAL BIOLOGY RECIPIENT LIST 2015 Investigator, Howard Hughes Medical Institute Rudolf Jaenisch, MD Whitehead Institute for Biomedical Research, For pioneering work in human cytogenetics and the normal and and Professor of Biology abnormal function and behavior of the X and Y chromosomes. Massachusetts Institute of Technology, Cambridge, MA 2010 For devising innovative technologies that elucidated long-standing Shinya Yamanaka, MD, PhD * dilemmas in developmental biology, for recognizing the L.K. Whittier Foundation Investigator in Stem Cell Biology transformative significance on cellular function of epigenetic Gladstone Institute of Cardiovascular Disease programming, and for applying the power of induced pluripotent Professor, University of California, San Francisco stem cells to novel discoveries. Director, Center for iPS Cell Research and Application 2014 For research on how certain master genes and protein signals regulate Huda Y. Zoghbi, MD formation and growth of organs such as the brain and limbs during Professor, Departments of Pediatrics; Molecular and Human Genetics; embryonic and fetal development. Neurology; Neuroscience; Programs in Cell and Molecular Biology and Developmental Biology 2009 Baylor College of Medicine, Houston, TX Kevin P. Campbell, PhD Carver Chair, Department of Molecular Physiology & Biophysics For pioneering work evolving from discovery that mutations in the X- Director of the Wellstone Muscular Dystrophy Cooperative Research linked MECP2 cause Rett syndrome and for studies elucidating the Center maintenance role of this epigenetic regulator in different neurons. Professor of Neurology and Internal Medicine 2013 University of Iowa, Roy J. and Lucille A. Carver College of Medicine, Eric Olson, PhD Iowa City, Iowa Annie and Willie Nelson Professorship in Stem Cell Research & Louis M.
    [Show full text]
  • The Origins of Oncomice: a History of the First Transgenic Mice Genetically Engineered to Develop Cancer
    Downloaded from genesdev.cshlp.org on October 2, 2021 - Published by Cold Spring Harbor Laboratory Press HISTORICAL PERSPECTIVE The origins of oncomice: a history of the first transgenic mice genetically engineered to develop cancer Douglas Hanahan,1,4 Erwin F. Wagner,2 and Richard D. Palmiter3 1Department of Biochemistry and Biophysics, Diabetes Center, and Comprehensive Cancer Center, University of California at San Francisco, San Francisco, California 94143, USA; 2Research Institute for Molecular Pathology (IMP), Vienna A-1030, Austria; 3Department of Biochemistry, University of Washington, Seattle, Washington 98195, USA This perspective describes the concurrent development cells within normal tissues of a mammalian organism in the 1980s of the first transgenic mice genetically en- could lead to tumor development. In 1992, gene knock- gineered to express dominant oncogenes, involving inde- out technology converged in a similar fashion with tu- pendent researchers who were largely unaware of each mor suppressor genetics in the generation of mice that other’s strategies and progress. We relate the experimen- developed cancers by virtue of lacking tumor suppressor tal designs, the pitfalls and challenges encountered, and gene function (for review, see Jacks 1996). the eventual success in developing distinctive mouse The significance of these early technological innova- models of cancer, wherein tumors arose heritably in vari- tions, which lead to genetically engineered mice en- ous organs. These early oncomice have produced a dowed to heritably develop particular forms of cancer, wealth of new knowledge, become topics of intellectual can be appreciated by considering the scientific/techni- property, and spawned a vibrant field of cancer research cal landscape then, and now.
    [Show full text]
  • Gail Roberta Martin (1944– ) [1]
    Published on The Embryo Project Encyclopedia (https://embryo.asu.edu) Gail Roberta Martin (1944– ) [1] By: Villarreal, Lance Keywords: Embryonic Stem Cells [2] In the twentieth and early twenty-first centuries, Gail Roberta Martin specialized in biochemistry ande mbryology [3], more specifically cellular communication and the development of organs. In 1981, she named any cell taken from inside a human embryo at the blastocyst [4] stage an “embryonic stem cell”. During development, an embryo goes through theb lastocyst [4] stage just before it implants in the uterus [5]. Embryonic stem cells [6] are useful for experiments because they are self-renewing and able to develop into almost any cell type in the body. Martin later identified a key chemical component in limb development and continues to study embryogenesis [7], or the growth of embryos over time. Martin’s work one mbryonic stem cells [8] has allowed scientists to further research and treat human diseases, and her study of how organs form has helped scientists learn about the healthy growth of embryos. Martin was born in New York City, New York on 2 April 1944. She received her Bachelor of Arts degree in zoology from the University of Wisconsin, Madison in Madison, Wisconsin, in 1964. In the late 1960s, Martin studied as a graduate student at the University of California at Berkeley [9] in Berkeley, California, and worked under Harry Rubin studying how the Rous sarcoma [10] virus affected chicken [11] cells’ genetic material, commonly known as DNA, or deoxyribonucleic acid. When injected in to chickens, the Rous sarcoma [10] virus causes tumors to develop.
    [Show full text]
  • PR 7Thannual Szent-Györgyi Prize for Progress in Cancer Research.Indd
    PRESS RELEASE Chinese Scientists Zhen-Yi Wang and Zhu Chen Awarded 7th Szent-Györgyi Prize for Progress in Cancer Research Acute Promyelocytic Leukemia: from Highly Fatal to Highly Curable BETHESDA, Maryland (January 24, 2012) - The National Foundation for Cancer Research announced today that Dr. Zhen-Yi Wang and Dr. Zhu Chen have been awarded the 7th annual Szent-Györgyi Prize for Progress in Cancer Research for their innovative research that led to the successful development of a new therapeutic approach to acute promyelocytic leukemia (APL). By combining traditional Chinese medicine with Western medicine, Drs. Wang and Chen have provided dramatic improvement in the fi ve-year disease-free survival rate of APL patients – from approximately 25 percent to 95 percent – making this therapy a standard of care for APL treatment throughout the world, and turning one of the most fatal diseases into a highly curable one. “I am so glad to see that the efforts we have devoted to research on leukemia these last several decades have led to solid clinical benefi ts to APL patients around world,” said Dr. Wang. “This award will inspire us as we continue our efforts to fi nd more effective therapies to treat cancers.” “This is a great honor for Dr. Wang and me; it is quite humbling to know that our respected colleagues from many scientifi c disciplines have selected us for this prestigious award,” said Dr. Chen, who also serves as China’s Minister of Health. “Scientists across the globe are working every day to cure cancer. I hope our work may continue to inspire others.” A clinical researcher at the Ruijin Hospital in Shanghai in the early 1980s, Dr.
    [Show full text]