Tumor biology [electronic resource] : regulation of cell growth, differentiation, and genetics in cancer

331 Pages·1996·30.3 MB·English

by  Tsiftsoglou, Asterios S., 1948-

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Series H: Cell Biology, Vol. 99
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Tumor Biology
Regulation of Cell Growth,
Differentiation and Genetics in Cancer
Edited by
Asterios S. Tsiftsoglou
Laboratory of Pharmacology
Department of Pharmaceutical Sciences
Aristotle University of Thessaloniki
Thessaloniki 54006, Greece
Alan C. Sartorelli
Department of Pharmacology
Yale University School of Medicine
333 Cedar Street
New Haven, CT 06510, USA
David E. Housman
Department of Biology
Center for Cancer Research
Massachusetts Institute of Technology
77 Massachusetts Avenue, E17-536
Cambridge, MA 02139, USA
T. Michael Dexter
Department of Experimental Hematology
Christie Hospital, NHS Trust
Paterson Institute for Cancer Research
Wilmslow Road
Manchester M20 9BX, UK
Springer
Published in cooperation with NATO Scientific Affairs Division
Proceedings of the NATO Science Institute "Regulation of Cell Growth,
Differentiation and Genetics in Cancer", held at Porto Carras, Halkidiki,
Greece, September 1-12,1995
Library of Congress Cataloging-in-Publication Data
Tumor biology: regulation of cell growth, differentiation, and
genetics in cancer I edited by Asterios S. Tsiftsoglou ... ret al.].
p. cm. -- (NATO ASI series. Series H, Cell biology; vol.
99)
'Proceedings of the NATO Science Institute "Regulation of Cell
Growth, Differentiation, and GenetiCS in Cancer," held at Porto
Carras. Halkidiki, Greece, September 1-12, 1995"--T.p. verso.
"Published in cooperation with NATO Scientific Affairs Division."
Includes bibliographical references and index.
1. Cancer cells--Congresses. 2. Cancer--Genetic aspects-
-Congresses. 3. Cancer--Molecular aspects--Congresses.
I. Tsiftsoglou. Asterios S., 1948- II. NATO Scientific Affairs
Organization. SC1entific AffaIrs Division. III. NATO SCIence
Institute "Regulation of Cell Growth, Differentiation, and Genetics
in Cancer" (1995 Chalkidik~, Greece) IV. Series.
[DNLM: 1. Neooiasms--genetics--congresses. 2. Cell Cycle-
-congresses. 3. Cell Differentiation--congresses. 4. Apoptosis-
-congresses. QZ 200 T911 1996J
RC254.6.T82 1996
616.99'407--dc20
DNLM/DLC
for Library of Congress 96-32244
CIP
ISBN-13: 978-3-642-64735-2 e-ISBN-13: 978-3-642-61180-3
001: 10.1007/978-3-642-61180-3
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© Springer-Verlag Berlin Heidelberg 1996
Softcover reprint of the hardcover 1s t edition 1996
Typesetting: Camera ready by authors/editors
Printed on acid-free paper
SPIN 10477178 31/3137 -5 4 3 210
FOREWORD
With the aim of providing an international forum for the communication of both
the basic and clinical aspects of molecular and cellular biology of cancer, a NATO
ASl was held in Porto Carras, Halkidiki, Greece, September 1-12, 1995. The
principles as well as recent developments in tumor biology were discussed in depth,
with emphasis on the regulation of the cell cycle, differentiation, programmed cell
death (apoptosis) and genetics of cancer. This book constitutes the proceedings of
that meeting.
Specifically, the following areas were addressed: (a) enzymes and proteins (cyclins)
that control the cell cycle, as well as the role of m as gene in meiosis and
transformation; (b) the structural basis for specificity in protein-tyrosine kinase
reactions; (c) the differentiation of normal as well as neoplastic cells with respect to
molecular mechanism(s) by which chemical agents or growth factors trigger
maturation; (d) phenotypic and genetic aspects of apoptosis; (e) the role of growth
factors, like IGF-l, FGF, TN, IL-6, etc., in cell cycle regulation, apoptosis (cell
death) and senescence; (f) molecular mechanisms of transcriptional activation of
globin genes and stability of mRNAs related to growth proteins and iron
metabolism; (g) the cellular and molecular biology of bone marrow hemopoiesis;
and (h) neurotrophic factors and the generation of cellular diversity in the central
nervous system.
It was obvious from the studies presented that neoplastic cell growth,
differentiation and apoptosis in many cell types are regulated at several levels.
These include (a) the membrane-mediated events which promote growth via signal
transduction pathways and activation of various genes, including oncogenes and
mutated tumor suppressor genes (e.g., p53, Rb); (b) transcription factors or
inducer-binding proteins that promote expression of a differentiated phenotype and
maturation of neoplastic cells; (c) growth factors which activate growth,
differentiation and/or cell death in hemopOietic, squamous epithelial cells and
neurons; and Cd) structural regulatory cis-elements that regulate transcription of
globin genes and stability of RNA transcripts.
Some of the lecturers and contributors presented the most recently developed
methodology to resolve questions related to signal transduction and transcriptional
activation. In addition, emphasis was given to transgenic and gene knockout animal
models bearing deletions in certain oncogenes and other genes as valuable systems
for examining the role of some genes in tumor development. The role of the p53
gene in the process of apoptosis induced by anticancer agents was discussed.
Finally, differentiation therapy with retinoids was presented as an alternative way
of treating patients with acute promyelocytic leukemia (APL).
The meeting was attended by selected participants from Belgium, Bulgaria, Canada,
Finland, France, Germany, Greece, Israel, Italy, Poland, Romania, Russia,
Switzerland, Turkey, United Kingdom and USA. Presentations by the guest
lecturers were followed by intense and insightful discussions, which continued
following the afternoon sessions (tutorials). Moreover, several interesting
contributions were made by participants who presented their work in such areas as
differentiation of epithelial cells and megakaryocytes, as well as apoptosis of colon
carcinoma cells.
VI
In summary, the participants in the Porto Carras meeting were exposed to both
fundamental and more advanced aspects of cancer research, which may have
potential application in their work. The Institute also provoked many new
questions regarding the regulation of cancer cells. Equally significant was the
opportunity for scientific interchange on a personal level, especially between
participants from East Europe and those from the NATO countries. We wish to
express our appreciation to the NATO Scientific Affairs Division for sponsoring
and financing the ASI, as well as the Greek Secretariat of Science and Technology
and the Greek National Tourist Organization (Central Macedonia Branch) for their
cooperation. We would also like to acknowledge Ms. Brenda Fasnacht for her
dedicated effort and efficiency in coordinating the conference.
The Editors
TABLE OF CONTENTS
LAP (NF-IL6) Modulates Hepatoma Cell Proliferation
M. Buck and M. Chojkier
The Structural Basis for Specificity in Protein-Tyrosine Kinase Signaling 5
L.c. Cantley and Z. Songyang
PML Is a Primary Target Gene of Interferon 17
and Could Mediate Some of Its Biological Activities
M.K. Chelbi-Alix, L. Pelicano. F. Quignon, M. Koken and H. de The
Differentiation Therapy of Acute Promyelocytic Leukemia 29
L. Degos
Biology of Haematopoietic Cell Growth Factors 39
T.M. Dexter
Mos, Meiosis and Cellular Transformation 59
K. Fukasawa, T. Choi and G.F. Vande Woude
Cell Cycle Regulation in Intestinal Epithelial Cells 73
AL. Ganel, Medeia GaneJ, E. Goufman and AL. Tyner
MG-160, a Sialoglycoprotein of the Medial Cisternae of the Golgi Apparatus, 81
Is Closely Related to a Receptor of Fibroblast Growth Factors
and to a Ligand of E-Selectin: Functional Implications
1.0. Gonatas, Y-J Chen, A Stieber, Z. MoureJatos and N.K. Gonatas
The Regulation of Human ~-Globin Gene Expression: 93
the Dynamics of Transcriptional Competition in the Human ~-Globin Locus
F. Grosveld, N. Dillon. P. Fraser, J. Strouboulis and M. Wijgerde
Post-Transcriptional Regulation of Iron Metabolism lOS
M.W. Hentze
The Control of Multiplication and Differentiation 113
in Human Myelomonocytic Leukemia Cells
F.R. Collan, D.A Tonetti and E. Hubennan
The Role of Oncogenes in the Integrated Control 129
of Cell Proliferation and Cell Death
B. S. Ink and G.I. Evan
Molecular Mechanisms Controlling Susceptibility 143
to Tumor Necrosis Factor Induced Cell Death
1. Klefstrom, E. SakseJa and K. AJitaJo
Cell-Cell Interactions in Osteoblastic Metastasis 155
Caused by Advanced Prostate Cancer
M. Koutsilieris
VIII
Apoptosis in Colonic Epithelium: a Message from the Crypt 167
S.A Lamprecht, S. Lifshitz, S.Polak -Charcon and B. Schwartz
Characterisation of a Retroviral Insertion Mutagenesis Protocol 177
to Obtain Mutants with Activated Apoptosis Inhibitory Genes
Y. Leverrier, 1. Thomas, M. Mangeney and 1. Marvel
Structure-Function Studies of Murine MIP-2, the Homologue of Melanoma 183
Growth Stimulating Activity/Gro-u and IL-8
E. Lolis and L.F. lerva
Effect of Retinoic Acid on CD14 Expression and the Intracellular Distribution 195
of Inositol Following LPS-Stimulation in U937 Cells
N. Menager and D. Rotondo
Regulation of the Proto-Oncogene Product c-Jun by Phosphorylation- 201
Mediated Intramolecular Signaling
AG. Papavassiliou
The Generation of Cellular Diversity in the CNS 207
1. Price
Stromal Cell Control of Haemopoiesis 227
1. Qiu and P.R. Harrison
The Insulin-Like Growth Factor I Receptor 235
and Its Role in Tumorigenesis and Cell Survival
M. Resnicofi and R. Baserga
Inhibition of Megakaryocyte Differentiation in Vivo by E2F-l 247
M. O. Robinson
Regulation of c-myc mRNA Half-Life by an RNA-Binding Protein 257
1. Ross, P. Bernstein, RD. Prokipcak and D.J. Herrick
Role of Intracellular Interleukin-6 273
in Growth Factor-Induced Cell Proliferation
M. Roth
Differentiation of Malignant Cells as a Therapeutic Approach 285
AC. Sarrorelli, K. Ishiguro, 1. Li, D.C. Koay and 1.A Sokoloski
Regulation of Murine Erythroleukemia Cell Differentiation 295
AS. Tsiftsoglou, IS. Vizirianakis and I Pappas
Expression of Tyrosine Kinases in the Mouse Small Intestine 309
AL. Tyner, V. Vasioukhin, M.S. Serfas, E. Y. Siyanova and X. Uor
The Discovery and Characterization 319
of Neurotrophic and Myotrophic Factors
G.D. Yancopoulos
Subject Index 329
lAP (NF-n.6) MODUIA'OO HEPAroMA CF1L PROLIFERATION
Martina Buck and Mario Chojkier
Department of Medicine and
Center for Molecular Genetics (9111-D)
University of California
San Diego, CA 92161
LAP, a liver-enriched activator protein, in addition to its role as a transactivator of liver-specific
genes (Descombes et aI., 1990; Poli et aI., 1990; Cao et aI., 1991; Williams et aI., 1991),
consistently arrests the progression of the cell cycle from G1 to S-phase in HepG2 hepatoma cells
(Buck et aI., 1994). Alternatively, LAP may induce entry of hepatoma cells into Go. In addition,
a relatively low LAPILIP ratio, as well as the disruption of the LAP leucine zipper, abolishes the
inhibitory effect of LAP on hepatoma cell proliferation. By contrast, ClEBPa did not affect HepG2
cell proliferation.
Unlike LAP, ClEBPa did not block HepG2 cell proliferation either in transient, or in stable
expression experiments. Both LAP and ClEBPa transactivate, as expected, an aIbumin promoter
CAT reporter gene. Although LAP and ClEBPa show an indistinguishable DNA-binding
specificity in vitro and readily heterodimerize, we suggested that by virtue of their divergent N
terminal domains LAP and ClEBPa would be likely to affect different target genes (Descombes et
aI., 1990). Although it is of great interest that LAP and ClEBPa may have different roles on
hepatic cell proliferation, other examples of their dissimilar biological fimctions have been fOlmd
(Wegner et aI., 1992; Poli et aI., 1990; Houglmn et aI., 1994).
In a series of experiments, we assessed the effect of various LAP constructs on the cell
cycle in order to characterize the structureIfimctional relationship. As expected, a deletion of 21
amino acids from the N-terminal domain, resulted in a protein expressed in normal liver
(Descombes et aI., 1990; Descombes and Sehibler, 1991), and did not affect the inhibitory activity
of LAP upon the cell cycle. Similarly, mutation of 4 amino acids on the basic DNA binding
domain (R238~G, K239 ~ T, S240~ P and R241~G), which inhibits binding to the cognate D-site of
the aIbumin promoter did not prevent the inhibition of cell proliferation by LAP. By contrast, an
intact DNA binding domain is required for ClEBPa to arrest adipocyte proliferation (Umek et aI.,
1991), suggesting that different mechanisms may be responsible for the inhibition of hepatoma cell
and adipocyte proliferation by LAP and ClEBPa, respectively.
NATO ASI Series, Vol. H 99
Tumor Biology
Regulation of Cell Growth. Differentiation and
Genetics in Cancer
Edited by Asterios S. TsiftsogIou. Alan C. Sartorelli,
David E. Housman and T. Michael Dexter
© Springer·V erlag Berlin Heidelberg 1996