Cell Transformation NATO ASI Series Advanced Science Institutes Series A series presenting the results of activities sponsored by the NA TO Science Committee, which aims at the dissemination of advanced scientific and technological knowledge, with a view to strengthening links between scientific communities. The series is published by an international board of publishers in conjunction with the NATO Scientific Affairs Division A Life Sciences Plenum Publishing Corporation B Physics New York and London C Mathematical D. Reidel Publishing Company and Physical Sciences Dordrecht, Boston, and Lancaster D Behavioral and Social Sciences Martinus Nijhoff Publishers E Engineering and The Hague, Boston, and Lancaster Materials Sciences F Computer and Systems Sciences Springer-Verlag G Ecological Sciences Berlin, Heidelberg, New York, and Tokyo Recent Volumes in this Series Volume 89-Sensory Perception and Transduction in Aneural Organisms edited by Giuliano Colombetti, Francesco Lenci, and Pill-Soon Song Volume 90-Liver, Nutrition, and Bile Acids edited by G. Galli and E. Bosisio Volume 91-Recent Advances in Biological Membrane Studies: Structure and Biogenesis, Oxidation and Energetics edited by Lester Packer Volume 92-Evolutionary Relationships among Rodents: A Multidisciplinary Analysis edited by W. Patrick Luckett and Jean-Louis Hartenberger Volume 93-Biology of Invertebrate and Lower Vertebrate Collagens edited by A. Bairati and R. Garrone Volume 94-Cell Transformation edited by J. Celis and A. Graessmann Series A: Life Sciences Cell Transformation Edited by J. Celis Aarhus University Aarhus, Denmark and A. Graessmann Institute for Molecular Biology Free University of Berlin Berlin, Federal Republic of Germany Plenum Press New York and London Published in cooperation with NATO Scientific Affairs Division Proceedings of a NATO Advanced Study Institute/FEBSI Gulbenkian Foundation Summer School on Cell Transformation, held September 2-12, 1984, in Sintra-Estoril, Portugal Library of Congress Cataloging in Publication Data NATO Advanced Study Institute/FEBS/Gulbenkian Foundation Summer School on Cell Transformation (1984: Sintra and Estoril, Portugal) Cell transformation. (NATO ASI series. Series A, Life sciences; v. 94) "Proceedings of a NATO Advanced Study Institute/FEBS/Gulbenkian Foundation Summer School on Cell Transformation, held September 2-12, 1984, in Sintra-Estoril Portugal"-T.p. verso. "Published in cooperation with NATO Scientific Affairs Division." Includes bibliographies and index. 1. Carcinogenesis-Congresses. 2. Oncogenes-Congresses. 3. Cancer-Genetic aspects-Congresses. I. Celis, J. E. (Julio E.) II. Graessmann, A. III. NATO Advanced Study Institute. IV. Federation of Euro pean Biochemical Societies. V. Fundac;:ao Calouste Gulbenkian. VI. North Atlantic Treaty Organization. Scientific Affairs Division. VII. Title. VIII. Series. [DNLM: 1. Cell Transformation, Neoplastic-congresses. 2. Cell Transforma tion, Viral-congresses. 3. Gene Expression Regulation-congresses. QZ 202 N2785c 1984) RC268.5.N345 1984 616.099'4071 85-16923 ISBN-13: 978-1-4684-5011-8 e-ISBN-13: 978-1-4684-5009-5 001: 10.1007/978-1-4684-5009-5 ©1985 Plenum Press, New York Softcover reprint of the hardcover 1st edition 1985 A Division of Plenum Publishing Corporation 233 Spring Street, New York, N.Y. 10013 All rights reserved No part of this book may be reproduced, stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming, recording, or otherwise, without written permission from the Publisher PREFACE This volume is based on the proceedings of a NATOjFEBSjGulbenkian Foundation sponsored Summer School held in September 1984 in Sintra Estoril, Portugal. Given the accelerated growth of knowledge in the field of cell transformation, it seemed timely to hold a summer school to discuss current developments in this area of biology as well as to evaluate emerging technology. The first article in this volume gives an evaluation of the various cellular systems to study neoplasia. Their properties as well as advantages and disadvantages are dis cussed. The second section deals with the role of oncogenes in cell transformation. Particular emphasis is given to the question of whether activated proto-one genes are cancer genes and to the func tions of oncogene products. The third part is dedicated to viruses and includes articles on papova viruses, Epstein-Barr virus, adeno virus, parvo viruses and HTLV. The fourth part deals with gene ex pression in normal and transformed cells while the concluding sec tion considers various aspects of gene regulation in eukaryotic cell s. vi PREFACE We wish to express our appreciation to Dr. Maria C. Lechner who provided valuable advice and help concerning the organization of this meeting. We are also indebted to Ms. Lisbeth Heilesen and Ms. Anne Mette Lygaard for typing the manuscripts and for their out standing administration of the meeting. J.E. Cel is February 1985 A. Graessmann CONTENTS NEOPLASTIC TRANSFORMATION SYSTEMS 1. Neoplastic Transformation Systems - Their Use In Study- ing Carcinogenesis ..................................... . A. Sivak & A.S. TU ONCOGENES 2. Are Activated Proto-one Genes Cancer Genes?............ 21 P.H. Duesberg, M. Nunn, N. Kan, D. Watson, P.H. Seeburg & T. Papas 3. Immunoglobulin Genes, Oncogenes, and Human 8-Cell Tumors. • • • • . • • • • . • . • • • • • • • • • • • . • • . • • • • . • • . • • • • • . • . • • . • . . 65 P.C. Nowell & C.M. Croce 4. The Functions of Oncogene Products...................... 79 T. Hunter 5. Identification and Localization of Phosphoproteins in v-one Transformed Fibroblasts by Means of Phospho- tyrosine Antibodies..................................... 97 P.M. Comoglio, D. Cirillo, M.F. Di Renzo, R. Ferraeini, F.G. Giancotti, S. Giordano, L. Naldini, G. Tarone & P.C. Marchisio VIRAL TRANSFORMATION 6. The Transformation Capacity of Early SV40 DNA Frag- ments..... ....................... ....................... 113 A. Graessmann & M. Graessmann vii viii CONTENTS 7. The Transforming Genes of Polyoma Virus................. 127 M. Rassoulzadegan & F. Cuzin 8. Papova Vi ruses and Cancer Genes......................... 135 C. Streuli & B.E. Griffin 9. Epstein-Barr Virus and Immortalisation of Epithelial Cells ................•.....•.......•........•........... 157 B.E. Griffin 10. Functional Domains of Purified Adenovirus Type C E1A Proteins............................................ 167 B. Krippl, B. Ferguson, N. Jones, M. Rosenberg, & H. Westphal 11. Parvoviruses and Cancer................................. 175 B. Hirt 12. HTLV in Adult T Cell Leukemia and Acquired Immune Deficiency Syndrome..................................... 185 P.S. Sarin GENE EXPRESSION IN NORMAL AND TRANSFORMED CELLS 13. Construction of Protein Databases for Comparison of Normal and Transformed Cells............................ 209 J.I. Garrels & B.R. Franza, Jr. 14. Cye1in (PCNA) is a Component of the Pathway(s) Leading to DNA Replication and Cell Division: A Role in DNA Replication?........................................... 223 J.E. Celis & A. Celis REGULATION OF GENE EXPRESSION 15. Regulation of Gene Expression in Developmental and Oncogenic Processes: The Albumin A1pha-Fetoprotein Locus in Mammals........................................ 239 J.M. Sala-Trepat, A. Po liard, I. Tratner, M. Poiret, M. Gomez-Garcia, A. Gal, J.L. Nahon, & M. Frain CONTENTS ix 16. Transcription Control in Eucaryotes-Enhancers and Promoters. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 267 B. Bouraahot, P. HerbomeZ & M. Yaniv 17. Controls of Gene Expression in Chemical Carcinogenesis: Role of Cytochrome P450 Mediated Mono-Oxygenases........ 285 M. c. Leahner Contri butors. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 313 Index. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 317 NEOPLASTIC TRANSFORMATION SYSTEMS - THEIR USE IN STUDYING CARCINOGENESIS Andrew Sivak & Alice S. Tu Biomedical Research and Technology Section Arthur D. Little, Inc •• Acorn Park Cambridge. Massachusetts 02140, USA INTRODUCTION The cellular systems to study neoplasia essentially stem from two sources. One is the observation that one can induce alterations in cellular phenotype in a culture of cells infected with tumorigenic DNA viruses (1). The second is the finding of Berwald and Sachs in 1963 (2,3) that early passage Syrian hamster embryo cells exhibited clonal morphology not seen in untreated cultures following exposure to a chemical carcinogen. While the work of Earle and his associates (4) beginning in the nineteen thirties had demonstrated changes in cell cultures treated wi th carci nogens. it was the protocol and results reported in 1963 (2,3) that provided a means to obtain quantitative and reproducibl e findings of morphological transformation of mammal ian cells induced by chemical carcinogens. Over the past two decades a considerable variety of systems have been described to study neo plastic transformation. Of these, several have been shown to have value as bioassays for the identification of carcinogens. The prop erties as well as the advantages and disadvantages of these assays have been reviewed in depth recently along with a presentation of the available data base on tested chemicals (5-9). Table 1 lists these assay types along with some basic characteristics.