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

RNA TUMOR VIRUSES, ONCOGENES, HUMAN CANCER AND AIDS: On the Frontiers of Understanding