Biology of the Mammary Gland

BIOLOGY OF THE MAMMARY GLAND ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY Editorial Board: NATHAN BACK, State University of New York at Buffalo IRUN R. COHEN, The Weizmann Institute of Science DAVID KRITCHEVSKY, Wistar Institute ABEL LAJTHA, N. S. Kline Institute for Psychiatric Research RODOLFO PAOLETTI, University of Milan Recent Volumes in this Series Volume 474 HYPOXIA: Into the Next Millennium Edited by Robert C. Roach, Peter D. Wagner, and Peter H. Hackett Volume 475 OXYGEN SENSING: Molecule to Man Edited by Sukhamay Lahiri, Nanduri R. Prabhakar, and Robert E. Forster, II Volume 476 ANGIOGENESIS: From the Molecular to Integrative Pharmacology Edited by Michael E. Maragoudakis Volume 477 CELLULAR PEPTIDASES IN IMMUNE FUNCTIONS AND DISEASES 2 Edited by Jürgen Langner and Siegfried Ansorge Volume 478 SHORT AND LONG TERM EFFECTS OF BREAST FEEDING ON CHILD HEALTH Edited by Berthold Koletzko, Olle Hernell, and Kim Fleischer Michaelsen Volume 479 THE BIOLOGY AND PATHOLOGY OF INNATE IMMUNITY MECHANISMS Edited by Yona Keisari and Itzhak Ofek Volume 480 BIOLOGY OF THE MAMMARY GLAND Edited by Jan A. Mol and Roger A. Clegg Volume 481 ELASTIC FILAMENTS OF THE CELL Edited by Henk L. Granzier and Gerald H. Pollack Volume 482 CHROMOGRANINS: Functional and Clinical Aspects Edited by Karen B. Helle and Dominique Aunis Volume 483 TAURINE 4: Taurine and Excitable Tissues Edited by Laura Della Corte, Ryan H. Huxtable, Giampetro Sgaragli, and Keith F. Tipton Volume 484 PHYLOGENETIC PERSPECTIVES ON THE VERTEBRATE IMMUNE SYSTEM Edited by Gregory Beck, Manickam Sugumaran, and Edwin L. Cooper A Continuation Order Plan is available for this series. A continuation order will bring delivery of each new volume immediately upon publication. Volumes are billed only upon actual shipment. For further information please contact the publisher. BIOLOGY OF THE MAMMARY GLAND Edited by Jan A. Mol Utrecht University Utrecht, The Netherlands and Roger A. Clegg Hannah Research Institute Ayr, Scotland, United Kingdom KLUWER ACADEMIC PUBLISHERS New York, Boston, Dordrecht, London, Moscow eBook ISBN: 0-306-46832-8 Print ISBN: 0-306-46414-4 ©2002 Kluwer Academic Publishers New York, Boston, Dordrecht, London, Moscow All rights reserved No part of this eBook may be reproduced or transmitted in any form or by any means, electronic, mechanical, recording, or otherwise, without written consent from the Publisher Created in the United States of America Visit Kluwer Online at: http://www.kluweronline.com and Kluwer's eBookstore at: http://www.ebooks.kluweronline.com Preface It is difficult to overstate the evolutionary and functional significance of mammary tissue in biology. Substantial progress has been made by researchers in various disciplines, particularly over the last fifteen years, towards realizing the potential of this tissue to yield powerful experimental models for morphogenesis and tissue development; for cellular differentiation; for the biosynthesis and secretion of proteins, lipids, small molecules and inorganic salts; and for the coordination and regulation of these processes. More recently, the possibility of exploiting the secretory epithelial cells of mammary tissue as "cell factories" has become a reality and the recombinant production by lactating animals of an increasing number of proteins, valuable both in the pharmaceutical and "nutraceutical" fields, is in progress or under development. The fable of the goose that laid the golden egg has given way to the reality of Dolly the sheep and latter-day Dollys yielding milks of staggeringly high value. Alongside this high-profile biotechnology, the traditional role for mankind of lactating ruminant animals remains, as a "renewable" source of foodstuffs for human consumption. Also in this sphere of agricultural production, genetic as well as nutritional technologies are under investigation and exploitation to optimize milk composition for various end-uses - for instance in food process and manufacture. The possibilities of deriving health benefit from the bioactive properties of some of the minor constituents of milk are emerging to counter the highly-publicized negative health impact of excessive consumption of saturated animal fats. In human nutrition and medicine, the mammary gland is both a source of nutrition to the neonate and of potential health threat to the adult female - breast cancer remains the major single cause of female mortality in most developed countries. v vi Preface For 3 days in the autumn of 1999 (September 16th-18th) a group of around 175 biologists, all sharing a common interest in the mammary gland, gathered together in Tours, France. Individual researchers within the group owed allegiance to many scientific traditions including those of cellular and developmental biology, biochemistry and molecular biology, nutrition, genetics, biotechnology and medicine. In all probability, this was the greatest number of mammary gland biologists ever to have assembled in a single location within Europe - perhaps, the world. The occasion for such a concentration of mammary tissue specialism was the first International Conference on the Biology of the Mammary Gland. The undoubted success of this conference, against a background of such disciplinary diversity, stands as a tribute to the success of the European networking project that gave rise to it. To trace back to the origin of the idea for the Tours conference it is necessary to explore the genesis of the COST Action (#825) on Mammary Gland Biology, since the two were conceptually interconnected from the beginning, although the location in Tours only emerged much later. For the benefit of readers not familiar with the European Union systems, structures and programmes for the Europe-wide support of science, COST is one of those acronymic programmes (for cooperation in the field of scientific and technical research). COST exists to nurture and support networks of scientists with the objective of stimulating scientific collaboration, cooperation and communication across, and somewhat beyond, the EU. The COST 825 seed was sown paradoxically far from Europe, in New Hampshire, in 1991. In the Spartan New England conditions of a Gordon Conference on Mammary Gland Biology, conversation among a group of scientists turned (certainly not for the first time in the distinguished history of the Gordon Conferences) to a consideration of an enigma - why do European scientists in this field apparently have to cross the Atlantic ocean to find the opportunity to meet together and to discuss shared interests? Michèle Ollivier-Bousquet was in the midst of this debate, and during the remaining days of the Gordon Conference, began discretely to speak with colleagues about her vision of a European Mammary Gland Biology group. The seed grew, and in 1994 a proposal from a consortium of European mammary gland biologists, led by Ollivier-Bousquet, was submitted to the EU COST New Actions Committee. In due course, Action #825 - Mammary Gland Biology - was officially inaugurated in June 1995, with initial support for 5 years. A core aim of the COST 825 network has been to bring together the different scientific traditions which, while sharing an interest in mammary gland biology, have historically remained separate and even remote from one another. The medical (breast cancer) and the agricultural (lactation and Preface vii animal production) traditions represent the extremes of this separation. As the end of the century approached, all the infrastructure of a mature network was well-established, under the umbrella of COST, through meetings, workshops, a newsletter, a web-site, mailing-lists, and a searchable database of workers in the field. It seemed a good moment to draw together the varied scientific threads of the network and to join with colleagues worldwide in attempting to define just where we had reached in the field of mammary gland biology and the directions in which we were heading. Thus, although the Tours Conference owed its existence to the COST European network, the contributions of scientists from many countries both inside and outside the EU/COST orbit, ensured that the dimensions of this defining moment were truly international. Collected together in this volume, the invited communications presented at the Tours International Conference on the Biology of the Mammary Gland give a unique glimpse of our understanding, at the cutting edge of a variety of disciplines, of this versatile and extraordinary tissue, at the birth of the twenty-first century. Jan Mol Roger Clegg April 2000 Acknowledgements The chapters collected together here give an account of the proceedings of the first International Conference on the Biology of the Mammary Gland. The generous financial support for this Conference by the following not-for- profit bodies is acknowledged: Conseil Régional de la Région Centre, France; European Union COST programme; International Union of Biochemistry and Molecular Biology; National Institute of Agricultural Research (INRA), France. In addition, the Conference enjoyed commercial sponsorship from Atelier Coperta, Gent, Belgium; Intervet International B.V., The Netherlands; Lipha Santé, France; Merck Sharp & Dohme- Chibret, France; Monsanto Services Int SA, Belgium; Rhône Poulenc Animal Nutrition, France; Roche Pharma, France. Numerous individual members of the COST Action for Mammary Gland Biology contributed to the success of the Conference; their inputs were ably co-ordinated by an Organizing Committee consisting of Antonella Baldi (Italy), Paul Edwards (UK), Anne-Marie Massart-Leen (Belgium), Michèle Ollivier-Bousquet (France), Armand Sanchez (Spain) and Dieter Schams (Germany). Finally, it was the job of the local organizer, Charles Couet, to translate the will of the Organizing Committee into the reality of a Conference - a task that he undertook with great zeal, efficiency and good humour, and with valuable support from the Université François Rabelais, Tours. The staff at the Centre Vinci, Tours, not only ensured that the day-to- day activities and facilities of the Conference ran without any hitches but also facilitated the collection of many of the manuscripts leading to this publication. ix x Acknowledgements The editors express their thanks to the contributors of individual chapters for their cooperation and to Joanna Lawrence of the London Office staff at Kluwer Academic/Plenum Publishers for her help and support in bringing this volume to publication. Contents Fibroblast Growth Factor Signalling and Cyclin D1 Function are Necessary for Normal Mammary Gland Development during Pregnancy 1 VERA FANTL, ANNA CREER, CHRISTIAN DILLON, JANINE BRESNICK, DAVID JACKSON, PAUL EDWARDS, IAN ROSEWELL AND CLIVE DICKSON Hepatocyte Growth Factor and Neuregulin in Mammary Gland Cell Morphogenesis 9 CATHERIN NIEMANN, VOLKER BRINKMANN, WALTER BIRCHMEIER Expression and Localization of Growth Factors during Mammary Gland Development 19 FRED SINOWATZ, DIETER SCHAMS, ANNETTE PLATH, SABINE KÖLLE Involvement of Growth Factors in the Regulation of Pubertal Mammary Growth in Cattle 27 PURUP, S., VESTERGAARD, M. AND SEJRSEN, K. Insulin-like Growth Factor Binding Protein-5 (IGFBP-5) Potentially Regulates Programmed Cell Death and Plasminogen Activation in the Mammary Gland 45 ELIZABETH TONNER, GORDON ALLAN, LULZIM SHKRETA, JOHN WEBSTER, C. BRUCE A. WHITELAW, DAVID J. FLINT xi