Ernst Schering Research Foundation Workshop 14 Apoptosis in Hormone-Dependent Cancers

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1 Ernst Schering Research Foundation Workshop 14 Apoptosis in Hormone-Dependent Cancers

2 Ernst Schering Research Foundation Workshop 14 Apoptosis in Hormone Dependent Cancers M. Tenniswood, H. Michna Editors With 59 Figures and 18 Tables Springer-Verlag Berlin Heidelberg GmbH

3 ISBN ISBN ( ebook) DOI / CIP data applied for This work is subject to copyright. All rights are reserved, whether the whole or part of the material is concerned, specifically the rights of translation, reprinting, reuse of illustrations, recitation, broadcasting, reproduction on microfilms or in any other way, and storage in data banks. Duplication of this publication or parts thereof is permitted only under the provisions of the German Copyright Law of September 9, 1965, in its current version, and pennission for use must always be obtained from Springer-Verlag Berlin Heidelberg GmbH. Viol-ations are liable for prosecution under the German Copyright Law. Springer-Verlag Berlin Heidelberg 1995 Originally published by Springer-Verlag Berlin Heidelberg New York in 1995 Softcover reprint of the hardcover 1st edition 1995 The use of general descriptive names, registered names, trademarks, etc. in this publication does not imply, even in the absence of a specific statement, that such names are exempt from the relevant protective laws and regulations and therefore free for general use. Product liability: The publishers cannot guarantee the accuracy of any information about dosage and application contained in this book. In every individual case the user must check such information by consulting the relevant literature. Typesetting: Data conversion by Springer-Verlag Printed on acid-free paper

4 Preface To be, or not to be, that is the question: Whether 'tis nobler in the mind to suffer The slings and arrows of outrageous fortune Or to take arms against a sea of troubles And by opposing end them? To die; to sleep: No more; and by a sleep to say we end... William Shakespeare, Hamlet (III.i) If we replace the word "opposing" with "apoptosing" in Hamlet's well-known soliloquy and read it in terms of cell biology, it is as if Shakespeare already appreciated the cell suicide process. This type of death, conceptualized as programmed cell death or apoptosis, is a physiological mechanism. Apoptosis contributes to the control of cell turnover and the elimination of cells in normal and (pre )neoplastic tissue both during organogenesis and in completely developed tissue. A complex molecular machinery governs proliferation and most probably a cascade of factors induces programmed cell death or apoptosis. The function of this cell suicide process is probably to delete cells with damaged DNA and its ubiquitous nature has only recently been realized, accounting theoretically for the broad range of application in medicine. Nevertheless, the question of why such a diverse panel of drugs would program cells to actively commit suicide has not been answered. Most interestingly, in seeking to improve the selectivity of cancer therapy, the fact that different cell types possess different thresholds at which they respond to damage with apoptosis seems to offer an attractive option. Thus, hormone-dependent tumor epithelial cells readily engage in apoptosis whereas hormone-independent tumor cells do not. And so, after a century of pharmacology, we are now entering the age of cell physiology in disease treatment.

5 VI Preface Fig. 1. The participants of the workshop. From left to right, first row: K. W. Colston, F. Vignon, N. Kyprianou, J. Welsh; second row: G. J. van Steenbrugge, P. S. Rennie, M. Tenniswood, G. Aumtiller, H. Michna; third row: P. R. Walker, K. Parczyk, W. Bursch, A. Menrad;fourth row: D. Henderson, M. Schneider, G. Vollmer Since the mechanism of apoptosis is unknown, the editors of this monograph thought it would be a challenge to bring experts together to present the latest findings, to foster scientific cooperation, and to coherently organize the known data on the subject of "apoptosis in hormone-dependent tumors." Whether the reader is knowledgable in the field of apoptosis or is looking for a quick way to catch up on the latest provocative ideas, the editors hope that this volume will provide valuable information. Martin Tenniswood Horst Michna

6 Table of Contents Hormonal Control of Prostatic Differentiation and Morphogenesis: The Impact of Apoptosis and Steroid Hormone Receptor Expression G. Aumiiller, P. M. Holterhus, W. Eicheler, H. Renneberg, M. Bacher, L. Konrad, H. Bonkhoff, F. Rauch, and H. G. Mannherz Apoptosis in Experimental Prostate Cancer G. J. van Steenbrugge, W. M. van Weerden, M. H. A. Oomen, C. M. A. de Ridder, T. H. van der Kwast, and F. H. Schroder Therapeutic Significance of Apoptosis in the Treatment of Androgen-Dependent and Androgen-Independent Prostate Cancer N. Kyprianou Apoptosis in Relation to Androgen Independence in Experimental and Clinical Prostate Cancer P. S. Rennie, N. Bruchovsky, K. Akakura, S. L. Goldenberg, M. Gleave, and L. Sullivan Active Cell Death and Cancer W. Bursch, B. Grasl-Kraupp, A. Ellinger, L. Torok, H. Kienzl, L. Miillauer, and R. Schulte-Hermann

7 VIII Table of Contents 6 Modulation of Apoptosis by Oncogenes P.R. Walker, L. Testolin, U. Armato, N. Marceau, H. Gourdeau, and M. Sikorska Tenascin and Extracellular Matrix: Possible Biological Implications During Regression and Carcinogenesis of the Prostate G. Vollmer, S. Schenk, and H. Michna Anti-Growth Factor Activity of Antiestrogens in Human Breast Cancer Cells: A Review F. Vignon and H. Rochefort Differentiation and Apoptosis as a Therapeutic Strategy for Hormone-Dependent Cancers H. Michna and K. Parczyk ,25 Dihydroxyvitamin D3: Coordinate Regulator of Active Cell Death and Proliferation in MCF-7 Breast Cancer Cells M. Simboli-Campbell and J. Welsh Vitamin D3 Derivatives and Breast Cancer K. W Colston, A. G. Mackay and S. Y. James The Role of Growth Factors and Extracellular Matrix Proteases in Active Cell Death in the Prostate M. Tenniswood, R. S. Guenette, D. Taillefer, and M. Mooibroek Subject Index Previous Volumes Published in this Series

8 List of Contributors K.Akakura Department of Urology, Chiba University, Chiba, Japan U.Armato Department of Histology and Embryology, Institute of Anatomy and Histology, University of Verona, Verona, Italy G. Aumiiller Department of Anatomy and Cell Biology, Philipps-Universitiit, Robert-Koch-StraBe 6, Marburg, Germany M.Bacher Department of Anatomy and Cell Biology, Philipps-Universitiit, Robert-Koch-StraBe 6, Marburg, Germany H. Bonkhoff Department of Pathology, Universitat des Saarlandes, Homburg-Saar, Germany N. Bruchovsky Department of Cancer Endocrinology, British Columbia Cancer Agency, University of British Columbia, 600 West 1Oth Avenue, Vancouver, B.C., Canada, V5Z 4E6 W. Bursch Institut fiir Tumorbiologie-Krebsforschung der Universitiit Wien, Borschkegasse 8a, 1090 Wien, Austria

9 X List of Contributors K. W. Colston Steroid Biochemistry Group, St. George's Hospital Medical School, London SW 17 ORE, UK W. Eicheler Department of Anatomy, Philipps-Universitat, Robert-Koch-StraBe 6, Marburg, Germany A. Ellinger Histologisch-Embryologisches Institut der Universitat Wien, Ordinariat II, SchwarzspanierstraBe 17, Wien, Austria M. Gleave Department of Cancer Endocrinology, British Columbia Cancer Agency, University of British Columbia, 600 West loth Avenue, Vancouver, B.C., Canada, V5Z 4E6 S. L. Goldenberg Department of Cancer Endocrinology, British Columbia Cancer Agency, University of British Columbia, 600 West loth Avenue, Vancouver, B.C., Canada, V5Z 4E6 B. Grasl-Kraupp Institut fiir Tumorbiologie-Krebsforschung der Universitat Wien, Borschkegasse 8a, 1090 Wien, Austria H. Gourdeau Apoptosis Research Group, Institute for Biological Sciences, National Research Council, Bldg M54, Montreal Road, Ottawa, Ontario, Canada KIA OR6 R. S. Guenette W. Alton Jones Cell Science Center, 10 Old Bam Road, Lake Placid, NY 12946, USA P. M. Holterhus Department of Anatomy, Philipps-Universitat, Robert-Koch-StraBe 6, Marburg, Germany

10 List of Contributors XI S. Y. James Steroid Biochemistry Group, St. George's Hospital Medical School, London SW 17 ORE, UK H. Kienzl Institut fiir Tumorbiologie-Krebsforschung der Universitat Wien, Borschkegasse Sa, 1090 Wien, Austria L. Konrad Department of Anatomy, Philipps-Universitat, Robert-Koch-StraBe 6, Marburg, Germany T. H. van der Kwast Department of Pathology, Erasmus University Rotterdam, P.O.Box 1738, 3000 DR Rotterdam, The Netherlands N. Kyprianou Division of Urology, Department of Surgery, University of Maryland Medical Center, 22, South Greene Street, Baltimore, MD 21201, USA A. G. Mackay Steroid Biochemistry Group, St. George's Hospital Medical School, London SW 17 ORE, UK H. G. Mannherz Department of Cell Biology, Philipps-Universitat, Robert-Koch-StraBe 6, Marburg, Germany N. Marceau Cancer Research Centre, University of Laval, Hotel Dieu de Quebec, Quebec, Canada H. Michna Research Laboratories, Schering AG, MiillerstraBe , Berlin, Germany M. Mooibroek W. Alton Jones Cell Science Center, 10 Old Barn Road, Lake Placid, NY 12946, USA

11 XII List of Contributors L. Miillauer Institut fiir Tumorbiologie-Krebsforschung der Universitat Wien, Borschkegasse 8a, 1090 Wien, Austria M. H. A. Oomen Department of Urology, Division of Urological Oncology, Erasmus University Rotterdam, P.O.Box 1738, 3000 DR Rotterdam, The Netherlands K. Parczyk Research Laboratories, Schering AG, MiillerstraBe , Berlin, Germany F. Rauch Department of Cell Biology, Philipps-UniversiUit, Robert-Koch-StraBe 6, Marburg, Germany H. Renneberg Department of Anatomy, Philipps-Universitat, Robert-Koch-StraBe 6, Marburg, Germany P. S. Rennie Department of Cancer Endocrinology, British Columbia Cancer Agency, University of British Columbia, 600 West loth Avenue, Vancouver, B.C., Canada, V5Z 4E6 C. M. A. de Ridder Department of Urology, Division of Urological Oncology, Erasmus University Rotterdam, P.O.Box 1738, 3000 DR Rotterdam, The Netherlands H. Rochefort University of Montpellier I, Department of Cell Biology and INSERM Unit 148 on "Hormones and Cancer", 60, rue de Navacelles, Montpellier, France S. Schenk Friedrich Miescher Institut, P.O. Box 2543, 4002 Basel, Switzerland

12 List of Contributors XIII F. H. Schroder Department of Urology, Division of Urological Oncology, Erasmus University Rotterdam, P.O.Box 1738, 3000 DR Rotterdam, The Netherlands R. Schulte-Hermann Institut fiir Tumorbiologie-Krebsforschung der Universitat Wien, Borschkegasse 8a, 1090 Wien, Austria M. Sikorska Apoptosis Research Group, Institute for Biological Sciences, National Research Council, Bldg M54, Montreal Road, Ottawa, Ontario, Canada KIA OR6 M. Simboli-Campbell W. Alton Jones Cell Science Center, 10 Old Barn Road, Lake Placid, NY 12946, USA G. J. van Steenbrugge Department of Urology, Division of Urological Oncology, Erasmus University Rotterdam, P.O.Box 1738, 3000 DR Rotterdam, The Netherlands L. Sullivan Division of Urology, University of British Columbia, 600 West loth Avenue, Vancouver, B.C., Canada, VSZ 4E6 D. Taillefer W. Alton Jones Cell Science Center, 10 Old Bam Road, Lake Placid, NY 12946, USA M. Tenniswood W. Alton Jones Cell Science Center, 10 Old Bam Road, Lake Placid, NY 12946, USA L. Testolin Department of Histology and Embryology, Institute of Anatomy and Histology, University of Verona, Verona, Italy

13 XIV List of Contributors L. Torok Institut fiir Tumorbiologie-Krebsforschung der Universitat Wien, Borschkegasse 8a, 1090 Wien, Austria F. Vignon University of Montpellier I, Department of Cell Biology and INSERM Unit 148 on "Hormones and Cancer", 60, rue de Navacelles, Montpellier, France G. Vollmer Institut fiir Biochemische Endokrinologie, Medizinische Universitat zu Liibeck, Ratzeburger Allee 160, Liibeck, Germany P.R. Walker Apoptosis Research Group, Institute for Biological Sciences, National Research Council, Bldg M54, Montreal Road, Ottawa, Ontario, Canada KIA OR6 W. M. van Weerden Department ofuro1ogy, Division of Urological Oncology, Erasmus University Rotterdam, P.O.Box 1738, 3000 DR Rotterdam, The Netherlands J. Welsh Department of Biochemistry, University of Ottawa, Faculty of Medicine, Ottawa, Ontario, Canada