Table Of ContentMolecular Biology of Prostate Cancer
Molecular Biology
of Prostate Cancer
Editors
M. Wirth · J. E. Altwein · B. Schmitz-Dräger · S. Kuptz
w
DE Walter de Gruyter
G
Berlin · New York 1998
Editors
Prof. Dr. M. Wirth Prof. Dr. B. Schmitz-Dräger
Universitätsklinikum Dresden Heinrich-Heine-Universität Düsseldorf
Klinik für Urologie Klinik für Urologie
Fetscherstr. 74 Moorenstr. 5
01307 Dresden 40225 Düsseldorf
Germany Germany
Prof. Dr. J. E. Altwein Dr. S. Kuptz
Krankenhaus der Barmherzigen Brüder Zeneca GmbH
Klinik für Urologie Forschung Onkologie/Endokrinologie
Romanstr. 93 Otto-Hahn-Straße
80639 München 68723 Plankstadt
Germany Germany
Die Deutsche Bibliothek — Cataloging-in-Publication-Data
Molecular biology of prostate cancer / ed. M. Wirth ... · Berlin ;
New York : de Gruyter, 1998
ISBN 3-11-016159-1
© Copyright 1998 by Walter de Gruyter GmbH Sc Co., D-10785 Berlin.
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Preface
Prostate cancer is one of the most common malignant diseases affecting men in the
western world. With an estimated number of 334 500 new cases in 1997 in USA
prostate cancer has displaced lung cancer from first place in the table of annual
incidence rates in men. The enormous significance which prostate cancer has acquired
is reflected in the increasing number of scientific publications.
1800
1600
1400
1200
1000
800
600
400
200
0
1988 1990 1992 1994 1996
Fig. 1 Number of publications on prostate cancer from 1988 to 1996.
Our knowledge however on the aetiology, the natural progress and the biological
potential of this tumor is insufficient. Even now the majority of patients have already
reached an advanced stage of the disease when it is diagnosed. In this stage prostate
cancer is principally incurable.
Molecular biology is one field of research which has developed very rapidly in recent
years. The knowledge gained on the function of tumor genes and tumor proteins has
contributed considerably to the understanding of molecular and cell biology basis of
malignant growths. Based on these principles new approaches to prevention, diagno-
sis and treatment of tumors are being developed. This however requires close co-
operation between the doctor and the pure researcher.
The challenges presented in the clinical urology and basic science of prostate cancer
make it necessary to follow new paths. Our idea was to organise a symposium in
which scientists and medical doctors introduce the newest biomolecular knowledge
in prostate cancer and discuss its significance for clinical use. To structure the abun-
dance of information we have divided the symposium into four sections. Session 1
was concerned with the molecular principles of the genesis of prostate cancer, the
involvement of oncogenes and tumor suppressor genes. Session II involved the
vi Preface
changes of cell-cell contacts, the defects in androgen receptors and their effect on
treatment with antiandrogens. Session III explained drug resistance mechanisms and
new therapeutic principles such as antiangiogenesis inhibitors, intermittent androgen
ablation and gene therapy. Session IV was concerned with the diagnosis of prostate
cancer, new procedures such as RT-PCR and possible new markers.
All contributions have been included in this book. They provide the reader with the
opportunity to consult the wealth of information while creating a basis for new ideas
and approaches in the research and treatment of prostate cancer. Only so is it possible
to discover new paths for the management of prostate cancer. This symposium has
been designed to provide the basis to further stimulate this evolution.
M. Wirth, J. E. Altwein, B. Schmitz-Dräger, S. Kuptz
Contents
Cytogenetic alterations in prostate cancer 1
G. Sauter
The regulation of prostatic growth 9
K. Griffiths
Current concepts of oncogenes in prostate cancer 23
D. M. Peebl
Tumour suppressor genes in prostate cancer 31
S. F. Brewster
The use of differential display PCR for the detection of new tumor suppressor
genes in prostate cancer 43
Ch. P. Pilarsky
Molecular alterations associated with prostate cancer development 53
M. J. G. Bussemakers, ]. A. Schalken
Dysfunction of the cell-cell adhesion complex in lethal prostate cancer 65
R. Paul, W. B. Isaacs, G. S. Bova
Heparan sulfate proteoglycans and prostate cancer: a conceptual framework 71
D. H. J. Schamhart, K.-H. Kurth
Androgen receptor mutations in prostate cancer 81
H. Klocker, Z. Culig, A. Hobisch, A. Hittmair, G. Bartsch, H. Peterziel,
A. C. Β. Cato
Antiandrogen binding to androgen receptors and the consequences 89
B. J. A. Furr
Expression of the MDR1 gene in prostate carcinoma 101
M. /. Siegsmund, Β. Schummer, A. Steidler, M. Greschner, K.-U. Köhrmann,
P. Alken
Human prostate cancer progression models and therapeutic intervention.... 107
L. W. K. Chung, C. Kao, R. A. Sikes, H. E. Zhau
Tumor angiogenesis: the VEGF signalling system is a novel target for prostate
cancer therapy 115
D. Marmé
viii Contents
Antimetastatic approaches to therapy of prostate cancer 125
R. Heicappell
Intermittent androgen supression: rationale and clinical experience 133
M. Gleave, N. Bruchovsky, S. L. Goldenberg, P. Rennie
Resistance to drug therapy in cancer: gene therapy approaches to overcome
anticancer drug resistance 145
Th. Licht
PSA RT-PCR: current status and future potential 155
W. /. Ellis, R. L. Vessella, S. W. Melchior, P. H. Lange
Special aspects of PSMA and PSA RT-PCR for the detection of disseminated
prostate cells 161
B. Schmidt, M. Bendhack, R. Ackermann, Β. ]. Schmitz-Dräger
Molecular forms of PSA, PSA density, age-/race-specific reference ranges, and
PSA velocity 169
M. C. Beduschi, R. Beduschi, ]. E. Oesterling
Reverse transcriptase-polymerase chain reaction assays used for molecular stag-
ing of prostate cancer patients 181
C. A. Olsson, R. Buttyan
Concluding remarks 201
]. E. Altwein
List of first-mentioned contributors
Prof. Dr. J. E. Altwein Prof. Dr. B. Furr
Krankenhaus der Barmherzigen Brüder Zeneca Pharmaceuticals
Abteilung für Urologie Mereside, Alderly Park
Romanstr. 93 Macclesfield
80639 München Cheshire, SK 10 4TG
Germany U. K.
Dr. M. Gleave
Dr. M. C. Beduschi
The University of British Columbia
The University of Michigan
Division of Urology, UBC
1500 East Medical Center Drive
910 West 10th Avenue
Ann Arbor, Michigan 48109
Vancouver, B. C. V5Z 4E3
USA
Canada
Dr. M. J. G. Bussemakers
Prof. Dr. K. Griffiths
University Hospital Nijmegen
University of Wales
Urology Research Laboratory (814 URL)
College of Medicine
PO Box 9101
Tenovus Cancer Research Centre
6500 HB Nijmegen
Tenovus Building, Heath Park
The Netherlands
Cardiff CF4 4XX
U. K.
Prof. Dr. S. F. Brewster
Churchill Hospital
PD Dr. R. Heicapell
Department of Urology
Universitätsklinikum Benjamin Franklin
Oxford OX3 7LJ
Urologische Klinik u. Poliklinik
U. K.
Hindenburgdamm 30
12200 Berlin
Dr. L. W. K. Chung
Germany
University of Virginia
Health Science Center Univ. Doz. Dr. H. Klocker
Department of Urology Universitätsklinik für Urologie
Medical Center Box 422 Anichstr. 35
Charlottesville, VA 22908 6020 Innsbruck
USA Austria
Dr. W. J. Ellis PD Dr. Th. Licht
University of Washington National Cancer Institute, DBS, NIH
School of Medicine Laboratory of Molecular Biology
Department of Urology Building 37, Room 1B23
Box 356510 37 Convent Drive, MSC 4255
Seattle, WA 98195-6510 Bethesda, MD 20892-4255
USA USA
χ List of first-mentioned contributors
Prof. Dr. D. Marmé PD Dr. G. Sauter
Universität Freiburg Kantonsspital Basel Universitätskliniken
Institut für Molekularmedizin Institut für Pathologie
Breisacher Str. 117 D Schönbeinstr. 40
79106 Freiburg 4003 Basel
Germany Switzerland
Prof. Dr. C. Olsson
Squier Urological Clinic
Dr. D. H. J. Schamhart
The Presbyterian Hospital
University of Amsterdam
161 Fort Washington Avenue
Department of Urology
New York, NY 10032
USA Meibergdreef 9
1105 AZ Amsterdam
Prof. Dr. R. Paul
The Netherlands
Urologische Klinik u. Poliklinik
der TU München
Klinikum Rechts der Isar Dr. Bettina Schmidt
Ismaninger Str. 22
Heinrich-Heine-Universität
81675 München
Klinik für Urologie
Germany
Moorenstr. 5
Prof. Dr. M. Peehl 40225 Düsseldorf
Stanford University Germany
Department of Urology
School of Medicine
Stanford, CA 94305-5118 Prof. Dr. M. J. Siegsmund
USA Universität Heidelberg
Fakultät für Klinische Medizin
Dr. Ch. P. Pilarsky
MetaGen GmbH Urologische Klinik d. Stadt Mannheim
Ihnestr. 63 Theodor-Kutzer-Ufer 1—3
14195 Berlin 68135 Mannheim
Germany Germany
