Table Of ContentCell 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.
