RNA TUMOR VIRUSES, ONCOGENES, HUMAN CANCER AND AIDS: On the Frontiers of Understanding
RNA TUMOR VIRUSES, ONCOGENES, HUMAN CANCER AND AIDS: On the Frontiers of Understanding
DEVELOPMENTS IN ONCOLOGY F.J. Cleton and J.W.I.M. Simons, eds.: Genetic Origins of Tumour Cells. 90-247-2272-1. J. Aisner and P. Chang, eds.: Cancer Treatment Research. 90-247-2358-2. B.W. Ongerboerde Visser, D.A. Bosch and W.M.H. van Woerkom-Eykenboom, eds.: Neuro-oncology:
Clinical and Experimental Aspects. 90-247-2421-X. K. Hellmann, P. Hilgard and S. Eccles, eds.: Metastasis: Clinical and Experimental Aspects.
90-247-2424-4. H.F. Seigler, ed.: Clinical Management of Melanoma. 90-247-2584-4. P. Correa and W. Haenszel, eds.: Epidemiology of Cancer of the Digestive Tract. 90-247-260 1-8. L.A. Liotta and I.R. Hart, eds.: Tumour Invasion and Metastasis. 90-247-2611-5. J. Banoczy, ed.: Oral Leukoplakia. 90-247-2655-7. C. Tijssen, M. Halprin and L. Endtz, eds.: Familial Brain Tumours. 90-247-2691-3. F.M. Muggia, C.W. Young and S.K. Carter, eds.: Anthracycline Antibiotics in Cancer. 90-247-2711-1. B.W. Hancock, ed.: Assessment of Tumour Response. 90-247-2712-X. D.E. Peterson, ed.: Oral Complications of Cancer Chemotherapy. 0-89838-563-6. R. Mastrangelo, D.G. Poplack and R. Riccardi, eds.: Central Nervous System Leukemia. Prevention and
Treatment. 0-89838-570-9. A. Polliack, ed.: Human Leukemias. Cytochemical and Ultrastructural Techniques in Diagnosis
and Research. 0-89838-585-7. W. Davis, C. Maltoni and S. Tanneberger, eds.: The Control of Tumor Growth and its Biological Bases.
0-89838-603-9. A.P.M. Heintz, C. Th. Griffiths and J.B. Trimbos, eds.: Surgery in Gynecological Oncology.
0-89838-604-7. M.P. Hacker, E.B. Double and!. Krakoff, eds.: Platinum Coordination Complexes in Cancer
Chemotherapy. 0-89838-619-5. M.J. van Zwieten, The Rat as Animal Model in Breast Cancer Research: A Histopathological Study of
Radiation- and Hormone-Induced Rat Mammary Tumors. 0-89838-624-1. B. Lowenberg and A. Hogenbeck, eds.: Minimal Residual Disease in Acute Leukemia. 0-89838-630-6. I. van der Waal and G.B. Snow, eds.: Oral Oncology. 0-89838-631-4. B. W. Hancock and A. M. Ward, eds.: Immunological Aspects of Cancer. 0-89838-664-0. K.V. Honn and B.F. Sloane. Hemostatic Mechanisms and Metastasis. 0-89838-667-5. K.R. Harrap, W. Davis and A.N. Calvert, eds.: Cancer Chemotherapy and Selective Drug Development:
0-89838-673-X. V.D. Velde, J.H. Comelis and P.H. Sugarbaker, eds.: Liver Metastasis. 0-89838-648-5. D.I. Ruiter, K. Welvaart and S. Ferrone, eds.: Cutaneous Melanoma and Precursor Lesions.
0-89838-689-6. S.B. Howell, ed.: Intra-Arterial and Intracavitary Cancer Chemotherapy. 0-89838-691-8. D.L. Kisner and I.F. Smyth, eds.: Interferon Alpha-2: Pre-Clinical and Clinical Evaluation.
0-89838-701-9.
RNA TUMOR VIRUSES, ONCOGENES, HUMAN CANCER AND AIDS: On the Frontiers of Understanding
Proceedings of the International Conference on RNA Tumor Viruses in Human Cancer, Denver, Colorado, June 10-14, 1984
edited by
Philip Furmanski Jean Carol Hager Marvin A. Rich
AMC Cancer Research Center Denver, Colorado
Martinus Nijhoff Publishing a member of the Kluwer Academic Publishers Group Boston/DordrechtiLancaster
Distributors for North America: Kluwer Academic Publishers 190 Old Derby Street Hingham, MA 02043
Distributors for all other countries: Kluwer Academic Publishers Group Distribution Centre P.O. Box 322 3300 AH Dordrecht THE NETHERLANDS
Library of Congress Cataloging in Publication Data
International Conference on RNA Tumor Viruses in Human Cancer (1984: Denver, Colo.) RNA tumor viruses, oncogenes, human cancer and AIDS.
(Developments in oncology) Includes bibliographies and index. I. Viral carcinogenesis-Congresses. 2. Viruses, RNA-Congresses. 3. Oncogenes-Congresses.
4. Acquired immune deficiency syndrome-Etiology-Congresses. 5. Cancer-Genetics aspects-Congresses. I. Furmanski, Philip, 1946- . II. Hager, Jean Carol, 1943- . III. Rich, Marvin A. IV. Title. V. Title: R.N.A. tumor viruses, oncogenes, human cancer and AIDS. VI. Series. [DNLM: I. Acquired Immunodeficiency Syndrome-etiology-congresses. 2. Neoplasms-etiology-congresses. 3. Oncogenes-congresses. 4. Retroviridae-congresses. WI DE998N / QW 166 I606r 1984] RC268.57.15731984 616.99'4071 84-25515 ISBN -13: 978-1-4612-9620-1 e-ISBN -13:978-1-4613-2583-3 DOl: 10.1007/978-1-4613-2583-3
Copyright©1985 by Martinus NijhoffPublishing, Boston Softcover reprint of the hardcover 1st edition 1985
All rights reserved. No part ofthis publication may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, mechanical, photocopying, recording, or otherwise, without written permission of the publisher, Martinus NijhoffPublishing, 190 Old Derby Street, Hingham, Massachusetts 02043.
DEDICATION
As in all scientific advances, the achievements that move us toward
a true understanding of the nature and cause of cancer through studies of
the RNA tumor viruses were made by standing on "the shoulders of giants".
This volume is dedicated to three individuals who, by their own germinal
discoveries in the laboratory and their unstinting efforts in the
promotion, support and coordination of research, were driving forces
behind much of the progress in this area.
Twenty-five years ago, they isolated the agents that comprise the
FMR group of murine leukemia viruses. Their discoveries stimulated an
effort involving hundreds of laboratories throughout the world, resulting
in thousands of scientific publications, each adding incrementally to our
knowledge of cancer development.
The importance of their findings is evidenced also by contributions
of the FMR viruses to such diverse areas as differentiation, immunology,
genetics, biochemistry and molecular biology.
But these eminent scientists served the cancer research effort in a
larger capacity -- the initiation, promotion and direction of the world
wide scientific battle against cancer.
v
vi
It is for their discoveries, their insights, their energies and their
accomplishments that this volume is dedicated to:
PIONEERS IN TUMOR VIROLOGY
Dr. Charlotte Friend
Disaovepep - The FPiend Mupine Leukemia Vipus
Professor and Director
Center for Experimental Cell Biology
Mount Sinai School of Medicine
Dr. John B. Moloney
Disaovepep - The Moloney Mupine Leukemia vipus
Former Associate Director for Viral Oncology,
Chairman, Virus Cancer Program,
Former Assistant Director
National Cancer Institute
Dr. Frank J. Rauscher, Jr.
Disaovepep - The Rausahep Mupine Leukemia Vipus
Former Director
National Cancer Institute,
Senior Vice President for Research
American Cancer Society
CONTENTS Dedication v Contributors XI
Preface xix
MOLECULAR GENETICS OF THE RNA TUMOR VIRUSES
1. Myc, a Genetic Element that is Shared by a Cellular Gene (proto-myc) and by Viruses with One (MC29) or Two (MH2) onc Genes
Takis S. Papas, Nancy C. Kan, Dennis K. Watson, James A. Lautenberger, Christos Flordellis, Kenneth P. Samuel, Ugo G. Rovigatti, Miltos C. Psallidopoulos, Richard Ascione and Peter H. Duesberg
2. Viral and Cellular los Gene 14 Inder M. Verma, Tom Curran, A. Dusty Miller and Charles Van Beveren
3. P21 ras Transforming Protein: Significance of the Carboxy Terminus 25
Berthe M. Willumsen and Douglas R. Lowy
4. Protein Phosphorylation of Tyrosine in Normal and Transformed Cells 41
Jonathan A. Cooper, Kathy Gould and Tony Hunter
5. Activation of a Gene Coding for a Normal Human Growth Factor to One with Transforming Properties 54
Stuart A. Aaronson and Keith C. Robbins
6. Cell Cycle Control of c-myc Expression 67 Kathleen Kelly, Brent Cochran, Charles Stiles and Philip Leder
ENDOGENOUS RETROVIRUS SEQUENCES IN HUMAN CELLS
7. A New Class of Human Endogenous Retroviral Genes 76 Robert Callahan, Ing-Ming Chiu, Toby Horn, Igbal Ali, Joan Robbins, Stuart Aaronson and Jeffrey Schlom
viii
8. Structure and Function of Human Endogenous Type C Retroviral DNAS 93
Arnold B. Rabson, Paul E. Steele, Roy Repaske and Malcolm A. Martin
9. ERV3, A Full-Length Human Endogenous Provirus: Sequence Analysis and Evolutionary Relationships 108
Catherine D. 0 'Connell and Maurice Cohen
MOLECULAR BIOLOGY OF HUMAN CANCERS
10. Molecular Basis of Human B Cell Neoplasia 116 Carlo M. Croce and Peter C. Nowell
11. Stage Specific Transforming Genes in Lymphoid Neoplasms 127 Mary-Ann Lane, Henry A. F. Stephens, Matthew B. Tobin and Kevin Doherty
12. Oncogenes Involved in Chronic Myelocytic Leukemia l33 Nora Heisterkamp, John R. Stephenson, Gerard Grosveld, Annelies de Klein and John Groffen
13. Monoclonal Antibodies Generated to a Synthetic Peptide Define ras Gene Expression at the Single Cell Level in Human Colon and Mammary Carcinomas 151
Ann Thor, Patricia Horan Hand, David Wunderlich, Maureen Weeks, Arnaldo Caruso, Raffaella Muraro and Jeffrey Schlom
14. Which Cancers are Caused by Activated proto-one Genes? 168 Peter H. Duesberg, Michael Nunn, Nancy Kan, Dennis Watson, Peter H. Seeburg and Takis Papas
HTLV ILA V, T-CELL LEUKEMIA AND AIDS
15. The Family of Human T-Cell Leukemia Viruses and Their Role in the Cause of T-Cell Leukemia and AIDS 191
Robert C. Gallo, George Shaw, Beatrice Hahn, Flossie Wong-Staal, Mikulas Popovic, Jorge Schupbach, M. G. Sarngadharan, Suresh Arya, S. Zaki Salah uddin and Marvin S. Reitz, Jr.
ix
16. A Novel Human Lymphotropic Retrovirus (LA V): New Data on its Biology and Role in AIDS 206
Luc Montagnier, Francoise Barre-Sinoussi, David Klatzmann, Jean-Claude Gluckman, Christine Rouzioux, Francoise Brun-Vezinet and Jean-Claude Chermann
17. Biology of Human T Cell Leukemia Viruses in Immunosuppression and AIDS 218
Max Essex
18. Human Retrovirus in Acquired Immunodeficiency Syndrome (AIDS) 232
Donald P. Francis, Cirilo D. Cabradilla, Paul M. F eorino and V. S. Kalyanaraman
19. Human RNA and DNA Oncogenic Viruses and Their Importance in Transmissible and Malignant Diseases 240
Guy de The
20. Human T-Cell Leukemia Virus (HTLV) Antibodies in Mycosis Fungoides and Leukemias and Lymphomas 247
B. I. Sahai Srivastava and Michiko Koga
21. Immunologic Functions and the Pathogenesis of the Acquired Immune Deficiency Syndrome (AIDS) 254
Charles H. Kirkpatrick, Kathleen C. Davis, Charles R. Horsburgh, Jr., Patricia E. Rickmann, David L. Cohn, Kent Penley, Franklyn N. Judson and Bruce S. Dobozin
EXPERIMENTAL MODEL SYSTEMS FOR THE STUDY OF HUMAN NEOPLASIA AND RELATED DISEASES
22. Experimental Studies of the Pathogenesis of Feline Leukemia Virus Infection 267
Edward A. Hoover
23. Feline Leukemia and Sarcoma Viruses 289 William D. Hardy, Jr.
x
24. Bovine Leukemia Virus: Past, Present and Future 306 Arsene Burny, Claudine Bruck, Dominique Couez, Jacqueline Deschamps, Jacques Ghysdael, Diane Gregoire, Richard Kettmann, Marc Mammerickx, Daniel Portetelle, Nancy Rice, Robert Stephens and Raymond Gilden
25. A New Messenger RNA Expressed by Bovine Leukemia Virus Infected Cells 318
Robert Z. Mamoun, Therese Astier-Gin, Richard Kettmann, Jacqueline Deschamps, Nicole Rebeyrotte and Bernard J. Guillemain
26. Primate Retroviruses and AIDS 332 Murray B. Gardner
27. Molecular Comparisons of the D-Type Retroviruses 338 Eric Hunter, Christopher S. Barker, James Bradac, Subatndra Chatterjee, Ron Desrosiers and John W. Wills
28. Woodchuck Hepatitis Virus and Hepatitis B Virus as Related to Known RNA and DNA Tumor Viruses and Hepatocellular Carcinoma 354
Charles E. Rogier, Morris Sherman and David A. Shafritz
29. Establishment of Virus-Negative Cell Lines Derived from Radiation- or Chemically-Induced T-Cell Lymphomas in NFS/N Mice, and Generation of Oncogenic Virus from These Cell Lines Following Infection of A Non-Oncogenic Ecotropic Virus 372
Kazuyoshi Yanagihara, Toshio Seyama and Kenjiro Yokoro
PERSPECTIVES
30. Perspectives and Prospects of Molecular Biology in the Control of Human Malignancies 382
Peter J. Fischinger
31. Implications for the Control of Human Cancer 392 John W. Berg
Index 399
CONTRIBUTORS
Stua~t A. Aa~onson, Laboratory of Cellular and Molecular Biology, National Cancer Institute, Bethesda, Maryland, 20205
IgbaZ AZi, Laboratory of Tumor Immunology and Biology, National Cancer Institute, Bethesda, Maryland, 20205
Su~e8h A~ya, Laboratory of Tumor Cell Biology, Division of Cancer Treatment, National Cancer Institute, Bethesda, Maryland, 20205
Richa~ Ascione, Laboratory of Molecular Oncology, National Cancer Institute, Frederick Cancer Research Facility, Frederick, Maryland, 21701
The~ese Astie~-Gin, INSERM U. 117, 229 crs de 1 'Argonne, 33076 Bordeaux, France
Ch~istophe~ S. Ba~ke~, Department of Microbiology, University of Alabama, Laboratory for Special Cancer Research, Birmingham, Alabama, 35294
F~coise Ba~~e-Sinoussi, Laboratory of Virology, Institut Pasteur, Paris, France
John w. Be~, Department of Epidemiology, AMC Cancer Research Center, Denver, Colorado, 80214; and Departments of Pathology, Biometrics and Preventive Medicine, University of Colorado School of Medicine, Denver, Colorado, 80262
James B~c, Laboratory for Special Cancer Research, Department of Microbiology, University of Alabama, Birmingham, Alabama, 35294
cZaudine B~ck, Department of Molecular Biology, University of Brussels, Genese, Belgium
F~ncoise B~un-Vesinet, Hopital Claude Bernard, Paris, France
A~8ene Bu~y, Faculty of Agronomy, Gembloux, and Department of Molecular Biology, University of Brussels, Genese, Belgium
ci~iZo D. Cab~iZZa, Division of Viral Diseases, Center for Infectious Diseases, Centers for Disease Control, Atlanta, Georgia, 30333
Robe~ caZZahan, Laboratory of Tumor Immunology and Biology, National Cancer Institute, Bethesda, Maryland, 20205
xi
APnaU10 Capuso, Laboratory of Tumor Immunology and Biology, National Cancer Institute, Bethesda, Maryland, 20205
Subatndpa Chattepjee, Laboratory for Special Cancer Research, Department of Microbiology, University of Alabama, Birmingham, Alabama, 35294
Jean-CUxude ChePmann, Department of Virology, Institut Pasteur, Paris, France
Ing-Ming Chiu, Laboratory of Tumor Immunology and Biology, National Cancer Institute, Bethesda, Maryland, 20205
Bpent Cochpan, Harvard Medical School, Boston, Massachusetts, 02115
Maupice Cohen, National Cancer Institute, Frederick Cancer Research Facility, Frederick, Maryland, 21701
David L. Cohn, Denver Disease Control Service, Denver Department of Health and Hospitals, Denver, Colorado, 80204-4507
Jonathan A. Coopep, The Salk Institute, San Diego, California, 92138
Dominique Couez, Department of Molecular Biology, University of Brussels, Genese, Belgium
Caplo M. Cpoce, The Wistar Institute of Anatomy and Biology, Philadelphia, Pennyslvania, 19104
Tom CUPPan, Molecular Biology and Virology Laboratory, The Salk Institute, San Diego, California, 92138
Kathleen C. Davis, Conrad D. Stephenson Laboratory for Research in Immunology, Department of Medicine, Nationa~ Jewish Hospital and Research Center, Denver, Colorado, 80206
Annelies de Klein, Department of Cell Biology and Genetics, Erasmus University, 3000 DR Rotterdam, The Netherlands
Guy de The, Centre National de la Recherche Scientifique, Universite Claude Bernard, Laboratoire D'Epidemiologie et Immunovirologie des Tumeurs, Faculty of Medicine Alexis Carrel, Rue G. Paradin, 69372 Lyon, Cedex 2, France
JacqueZine Deschamps, ULB, Department Chimie Biologique, 1640 Rhode-SteGenese, Belgique; and Laboratory of Molecular Biology, University of Brussels, Genese, Belgium
Ron Desposieps, Laboratory for Special Cancer Research, Department of Microbiology, University of Alabama, Birmingham, Alabama, 35294
Bpuce S. Dobozin, Conrad D. Stephenson Laboratory for Research in Immunology, Department of Medicine, National Jewish Hospital and Research Center, Denver, Colorado, 80206
x~i
Kevin Dohepty, Laboratory of Molecular Immunobiology, Dana-Farber Cancer Institute, Boston, Massachusetts, 02115
Petep H. Duesbepg, Department of Molecular Biology and Virus Laboratory, University of California, Berkeley, California, 94720
Max Essex, Department of Microbiology, Harvard School of Public Health, Boston, Massachusetts, 02115
Paul M. Feopino, Division of Viral Diseases, Center for Infectious Diseases, Centers for Disease Control, Atlanta, Georgia, 30333
Petep J. Fischingep, National Cancer Institute, Bethesda, Maryland, 20205
Chpistos Flopdellis, Laboratory of Molecular Oncology, National Cancer Institute, Frederick Cancer Research Facility, Frederick, Maryland, 21701
Donald P. Fpancis, Division of Viral Diseases, Center for Infectious Diseases, Centers for Disease Control, Atlanta, Georgia, 30333
Robept C. Gallo, Laboratory of Tumor Cell Biology, Division of Cancer Treatment, National Cancer Institute, Bethesda, Maryland, 20205
Muppay B. GaPdnep, Department of Pathology, University of California, Davis, California, 95817
Jacques GhysdaeZ, Laboratory of Molecular Biology, University of Brussels, Genese, Belgium
Raymond Gilden, National Cancer Institute, PRI-Frederick Cancer Research Facility, Frederick, Maryland, 21701
Jean-Claude Gluckman, U.E.R. Pitie-Salpetriere, Paris, France
Kathy Gould, The Salk Institute, San Diego, California, 92138
Diane Gpegoipe, Laboratory of Molecular Biology, University of Brussels, Genese, Belgium
John Gpoffen, Oncogene Science Inc., Mineola, New York, 11501
Gepapd Gposveld, Department of Cell Biology and Genetics, Erasmus University, 3000 DR Rotterdam, The Netherlands
Bepnapd J. Guillemain, INSERM U. 117,229 crs de 1 'Argonne, 33076 Bordeaux, France
Beatpice Hahn, Laboratory of Tumor Cell Biology, Division of Cancer Treatment, National Cancer Institute, Bethesda, Maryland, 20205
Patpicia Hopan Hand, Laboratory of Tumor Immunology and Biology, National Cancer Institute, Bethesda, Maryland, 20205
William D. HaPdy, Jp., Laboratory of Veterinary Oncology, Memorial Sloan Kettering Cancer Center, New York, New York, 10021
xiv
No~ Heiste~kamp, Oncogene Science Inc., Mineola, New York, 11501
EdwaPd A. Hoove~, Department of Pathology, College of Veterinary Medicine and Biomedical Science, Colorado State University, Fort Collins, Colorado, 80523
Toby HoPn, Laboratory of Tumor Immunology and Biology, National Cancer Institute, Bethesda, Maryland, 20205
Cha~Zes R. Ho~sbu~gh, J~., Conrad D. Stephenson Laboratory for Research in Immunology, Department of Medicine, National Jewish Hospital and Research Center, Denver, Colorado, 80206
E~c Hunte~, Laboratory for Special Cancer Research, Department of Microbiology, University of Alabama, Birmingham, Alabama, 35294
Tony Hunte~, The Salk Institute, San Diego, California, 92138
F~nkZyn N. Judson, Denver Disease Control Service, Denver Department of Health and Hospitals, Denver, Colorado, 80204-4507
v. S. KaZyana~n, Division of Viral Diseases, Center for Infectious Diseases, Centers for Disease Control, Atlanta, Georgia, 30333
Nanc~ C. Kan, Laboratory of Molecular Oncology, National Cancer Instltute, Frederick Cancer Research Facility, Frederick, Maryland, 21701
KathZeen KeZZy, Immunology Branch, National Cancer Institute, Bethesda, Maryland, 20205
RichaPd Kettmann, ULB, Department Chimie Biologique, 1640 Rhode-SteGenese, Belgium; Faculty of Agronomy, Gembloux; and Department of Molecular Biology, University of Brussels, Genese, Belgium
Cha~Zes H. Ki~kpat~ick, Conrad D. Stephenson Laboratory for Research in Immunology, Department of Medicine, National Jewish Hospital and Research Center, Denver, Colorado, 80206
David KZatsmann, U.E.R. Pitie-Salpetriere, Paris, France
Michiko Koga, Roswell Park Memorial Institute, Buffalo, New York, 14263
Ma~y-Ann Lane, Laboratory of Molecular Immunobiology, Dana-Farber Cancer Institute, and Harvard Medical School, Boston, Massachusetts, 02115
James A. Lautenbe~ge~, Laboratory of Molecular Oncology, National Cancer Institute, Frederick Cancer Research Facility, Frederick, Maryland, 21701
PhiZip Lede~, Department of Genetics, Harvard Medical School, Boston, Massachusetts, 02115
DougZas R. Lowy, Laboratory of Cellular Oncology, National Cancer Institute, Bethesda, Maryland, 20205
xv
Ma~c MammePickx, National Institute for Veterinary Research, Uccle, Belgium
Robe~t z. Mamoun, INSERM U. 117,229 crs de 1 'Argonne, 33076 Bordeaux, France
MaZaoZm A. Marlin, Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, 20205
A. Dusty Mille~, Molecular Biology and Virology Laboratory, The Salk Institute, San Diego, California, 92138
Luc Montagnie~, Department of Virology, Institut Pasteur, Paris, France
Raffaella Mu~~o, Laboratory of Tumor Immunology and Biology, National Cancer Institute, Bethesda, Maryland, 20205
Pete~ c. Nowel~ Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, 19104
Michael Nunn, The Salk Institute, San Diego, California, 92138
cathe~ine D. O'ConneZ~ National Cancer Institute, Frederick Cancer Research Facility, Frederick, Maryland, 21701
Takis S. Papas, Laboratory of Molecular Oncology, National Cancer Institute, Frederick Cancer Research Facility, Frederick, Maryland, 21701
Kent PenZey, Denver Disease Control Service, Denver Department of Health and Hospitals, Denver, Colorado, 80204-4507
Mikulas Popovic, Laboratory of Tumor Cell Biology, Division of Cancer Treatment, National Cancer Institute, Bethesda, Maryland, 20205
Daniel Po~etelle, Faculty of Agronomy, Gembloux; and Department of Molecular Biology, University of Brussels, Genese, Belgium
Miltos C. PsalZidopoulos, Laboratory of Molecular Oncology, National Cancer Institute, Frederick Cancer Research Facility, Frederick, Maryland, 21701
A~oZd B. Rabson, Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Hea'lth, Bethesda, Maryland, 20205
NicoZe Rebey~otte, INSERM U. 117,229 crs de 1 'Argonne, 33076 Bordeaux, France
Ma~vin S. Reitz, J~., Laboratory of Tumor Cell Biology, Division of Cancer Treatment, National Cancer Institute, Bethesda, Maryland, 20205
xvi
Roy Repaske, Laboratory of Molecular t4icrobiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, 20205
Nancy Rice, National Cancer Institute, LBI-Frederick Cancer Research Facility, Frederick, Maryland, 21701
Patpicia E. Rickmann, Conrad D. Stephenson Laboratory for Research in Immunology, Department of Medicine, National Jewish Hospital and Research Center, Denver, Colorado, 80206
Joan Robbins, Laboratory of Tumor Immunology and Biology, National Cancer Institute, Bethesda, Maryland, 20205
Keith c. Robbins, Laboratory of Cellular and r~olecular Biology, National Cancer Institute, Bethesda, Maryland, 20205
Chaples E. Roglep, Liver Research Center and Departments of Medicine and Cell Biology, Albert Einstein College of i~edicine, Bronx, New York, 10461
chpistine Rouzioux, Hopital Claude Bernard, Paris, France
Ugo G. Rovigatti, Laboratory of f40lecular Oncology, National Cancer Institute, Frederick Cancer Research Facility, Frederick, Maryland, 21701
S. Zaki SaUxhuddin, Laboratory of Tumor Cell Biology, Division of Cancer Treatment, National Cancer Institute, Bethesda, Maryland, 20205
Kenneth P. Samuel, Laboratory of r'lolecular Oncology, fJational Cancer Institute, Frederick Cancer Research Facility, Frederick, Maryland, 21701
M. G. SaPngadhapan, Laboratory of Tumor Cell Biology, Division of Cancer Treatment, National Cancer Institute, Bethesda, Maryland, 20205
Jeffpey Schlom, Laboratory of Tumor Immunology and Biology, National Cancer Institute, Bethesda, Maryland, 20205
Jopge schupbach, Laboratory of Tumor Cell Biology, Division of Cancer Treatment, National Cancer Institute, Bethesda, Maryland, 20205
Petep H. Seebupg, Genentech, Inc., South San Francisco, California, 90007
Toshio Seyama, Research Institute for Nuclear t~edicine and Biology, Hiroshima University, Hiroshima 734, Japan
David A. Shafpitz, Liver Research Center and Departments of Medicine and Cell Biology, Albert Einstein College of i4edicine, Bronx, Ne\~ York, 10461
Geopge Shaw, Laboratory of Tumor Cell Biology, Division of Cancer Treatment, National Cancer Institute, Bethesda, Maryland, 20205
Moppis shepman, Liver Research Center and Departments of rledicine and Cell Biology, Albert Einstein College of Medicine, Bronx, New York, 10461
xvii
B. I. Sahai S~ivastava, Roswell Park Memorial Institute, Buffalo, New York, 14263
Paul E. Steele, Laboratory of i401ecular 14icrobiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health Bethesda, Maryland, 20205
Hen~y A. F. Stephens, Laboratory of r"lolecular Immunobiology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts, 02115
Robe~t Stephens, i~ational Cancer Institute, LSI-Frederick Cancer Research Facility, Frederick, Maryland, 21701
John R. Stephenson, Oncogene Science Inc., Mineola, New York, 11501
ChaY'les Stiles, Harvard Medical School, Boston, r1assachusetts, 02115
Ann ThoY', Laboratory of Tumor Immunology and B i 01 ogy, Nati onal Cancer Institute, Bethesda, Maryland, 20205
Matthew B. Tobin, Laboratory of i401ecular Immunobiology, Dana-Farber Cancer Institute, Boston, Massachusetts, 02115
chaY'Zes Van BeveY'en, Molecular Biology and Virology Laboratory, The Salk Institute, San Diego, California, 92138
Inde~ M. Vel"l11a, !,Iolecular Biology and Virology Laboratory, The Salk Institute, San Diego, California, 92138
Dennis K. Watson, Laboratory of Molecular Oncology, National Cancer Institute, Frederick Cancer Research Facility, Frederick, Maryland, 21701
Mau~een Weeks, National Cancer Institute, Bethesda, Maryland, 20205
John w. wills, Department of t~icrobiology, University of Alabama, Laboratory for Special Cancer Research, Rirminghal1, .A.labama, ?5294
BeY'the M. Willumsen, LJniversity of Copenhagen, Microbiology.Institute, Copenhagen, Denmark
Flossie Wong-Staal, Laboratory of Tumor Cell Biology, Division of Cancer Treatment, National Cancer Institute, Bethesda, Maryland, 20205
David Wunde~Zieh, National Cancer Institute, Rethesda, Maryland, 20205
Kazuyoshi Yanagiharu, Research I nstitute for i~ucl ear Medi ci ne and Biology, Hiroshima University, Hiroshima 734, Japan
KenjiY'o YokoY'o, Research Institute for Nuclear r1edicine and Biology, Hiroshima University, Hiroshima 734, Japan
PREFACE
We stand today on the threshold of a new understanding of cancer.
Primarily through the powerful tools of molecular biology, unified
hypotheses explaining the origins of the disease are emerging and rapidly
being validated. This volume, which presents the latest findings from
laboratories throughout the world on the role of RNA tumor viruses in
cancer, is a celebration of these achievements and a prediction of further
progress leading ultimately to the control of the disease.
It is important in this context to recall the natural history or life
cycle of RNA cancer virology. From the earliest days of the science, when
viruses were first recognized as distinct biologic agents of etiologic
significance, their role in cancer was proposed and hotly debated. The
critical early discoveries, even those made as recently as 25 years ago,
were met with rejection; not skepticism or cautious restraint, but
outright rejection. During the 60's, there was a gradual acceptance of
the association between viruses and cancer, the result of landmark studies
in experimental systems, and this led to a frenzy of activity in the
field. There followed another period of doubt and uncertainty, due
to the difficulty in attempting to apply directly, and in retrospect
inappropriately, the tenets of infectious disease to human cancers, only
to have the field resurrected, revitalized and redirected by the explosion
of progress in molecular biology and genetics.
Until this renaissance in RNA tumor virology, a unified explanation
for the origin of cancer was beyond our reach. But now we are approaching
a true molecular understanding of malignant transformation. Very much of
this quantum leap forward has been made possible by the contributors to
this volume.
xix
xx
Yet major questions remain to be answered. We must turn these same
tools of molecular biology and tumor virology, so valuable in dissecting
and analyzing the causes of cancer, to the task of understanding other
equally critical aspects of the cancer problem: progression, heterogeneity
and the metastatic process. These are absolutely crucial to our solving
the clinical difficulties of cancer: detection, diagnosis and effective
treatment. Thus, our intent is that this volume, in addition to presenting
the state-of-the-art in RNA tumor virology, will serve as a stimulus to
those in the field and others interested in the pathophysiology of cancer
for the attack and resolution of these problems. It is through these
efforts that we will achieve our final goal -- the complete control of
cancer.
We gratefully acknowledge assistance in the preparation of this
volume by Susan Guyer, Cathrine Allen and Carol Rains, and the generous
support of the AMC Cancer Research Center and the National Institutes of
Health through grant CA-38586 from the National Cancer Institute.
Philip Furmanski
Jean Carol Hager
Marvin A. Rich
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