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Raging Hormones in Development and Cancer
Cell 476
1997). The work on RNA localization does nothing less than offer a new vocabulary for thinking about transcription as it applies to cell polarity. These experiments demonstrate that the advanced microscopy techniques now available will contribute as much to our understanding of polarity as the molecular analyses of the last decade. Frank Solomon Massachusetts Institute of Technology Center for Cancer Research Cambridge, Massachusetts 02139
Raging Hormones in Development and Cancer Hormones and Growth Factors in Development and Neoplasia By Robert B. Dickson and David S. Salomon New York: Wiley (1998). 461 pp. $125.00 Have you ever wondered how a witch’s brew can transform a handsome prince into a toad or, as a colleague recently pleaded, how an angelic twelve-year-old daughter suddenly becomes a “hormonally challenged” teenager? Indirectly, Robert Dickson and David Salomon take on these questions in their recent book Hormones and Growth Factors in Development and Neoplasia. Specifically, they ask how signaling molecules such as hormones and growth factors lead to profound changes during development and ponder why these same molecules are implicated in prevalent cancers, such a breast, ovary, prostate, and others. In doing so they have provided a unique book that integrates our current understanding of hormone/growth factor signaling with invertebrate and vertebrate model systems in development and disease. While there are some obvious shortcomings in this initial undertaking to integrate very diverse fields, the editors have compiled an excellent set of chapters, some of which are especially relevant for those working in the area of reproduction. Indeed, the editors chose deliberately to emphasize reproduction because of the prominent role of hormones and growth factors in both pre- and postnatal reproductive development and because today human cancers are so prevalent in reproductive tissues. The contents of this book are broken into four sections. The first restricts its discussion to hormones and growth factors in invertebrate model systems; as a whole this section is extremely well written and is probably the best aspect of the book. The second section follows by detailing how growth factors influence mammalian development. In the third and more specialized section, postnatal developmental processes are discussed, in particular, reproductive tract and mammary gland development. The fourth and largest section provides a series of exciting perspectives on the known roles of hormones and growth factor signaling in tumor progression. For the uninitiated who might be drawn to
this book by its snappy cover and title, an overview and introductory chapter won’t be found. Even sophisticated readers might have benefited from some simple schematics summarizing the various signaling pathways discussed in the subsequent chapters. A brief overview of hormone action outlining the classes of growth factors, polypeptide hormones, steroid hormones, and their receptors would have been appreciated. Nonetheless, despite this omission, many of the chapters do provide a cogent and concise introduction in their particular area of interest. As with most multi-authored books, some chapters are superb while others are not—we will highlight those that fall into the former category. The first and, perhaps, one of the best sections of the book offers some illustrative examples of how hormones and growth factors affect invertebrate development. All of these chapters are well organized, well written, and informative. One could speculate that the consistent quality of this section stems from the ability to exploit these powerful genetic systems. For those of us entrenched in mammalian systems, lessons learned from the genetic pathways described for Drosophila and Caenorhabditis elegans prove to be extremely instructive. For example, the chapter by Bier elegantly describes the convergence of two signaling pathways, the tyrosine kinase (EGF-R) and TGF-b pathways, in early neurogenesis and wing vein development in Drosophila. From these two developmental events we learn that both synergy and antagonism occur between the EGF-R and TGF-b pathways. This cell-dependent divergence of shared signaling cascades may contribute to different stages of tumor formation in vertebrates. Segraves provides an outstanding chapter on steroid action in larval molting and metamorphosis in Drosophila. These dramatic developmental processes serve to underscore how one signaling hormone, such as ecdysone, initiates different developmental programs of gene expression in multiple tissues. Indeed, it is this very question that underlies so much of the current scientific inquiry into nuclear receptor function and hormone action. Interestingly, we still do not know the molecular identity of one important component of metamorphosis, the juvenile hormone receptor in Drosophila. Moreover, with the recent discovery of z200 putative orphan nuclear receptors in C. elegans via the genome project, assigning a ligand with its bona fide receptor will continue to pose a serious challenge to those in the steroid/hormone nuclear receptor field. Although many of the chapters describing the mammalian model systems are less refined, genetic studies conducted within the last several years are beginning to provide a more comprehensive picture, at least in mice. The roles of growth factors in early mammalian development are summarized in the chapter by Rappolee, which offers an up-to-date review of all factors known to affect both pre- and postimplantation. An excellent chapter by Yarden and others summarizes current data on the complex network of ligand and receptors in tyrosine kinase signaling. After reading this chapter (which is quite useful for subsequent chapters in the fourth section), it is apparent that much work has yet to be done to break the complex signaling code of this remarkable family of growth factors. Chapters
Book Reviews 477
discussing the role of hormones and growth factors in postnatal development focus primarily on reproductive tract and mammary gland development. Here, these biological systems demonstrate that any cell–cell communication (i.e., autocrine and paracrine signaling) can be considered to be hormone action. This broader definition is nicely illustrated in Cunha’s chapter on reproductive tract development and in the two chapters describing prolactin signaling in mammary gland development by Hennighausen and Vonderhaar. In considering how hormones influence reproductive development, a relevant topic that was not formally covered in this section, but was mentioned, is the subject of endocrine disrupters. There is growing concern (and controversy) about the potential of environmental agents, mimicking hormones, to cause developmental defects in humans and wildlife. Since hormone responsiveness in the embryo may be fundamentally different from that in the adult (reviewed in Limbard, L., and Taylor, P. Cell, 157–163, 1998), endocrine disrupters could potentially provide a tool to dissect hormone signaling in development and neoplasia from signaling in normal adult physiology. Perhaps, the second edition of this book will include a dedicated chapter devoted to this important issue. The final section of this book focuses on current research detailing the roles of sex steroids, peptide hormones, and growth factors in formation and progression of human cancers. In a number of these reviews, the prominent role of steroids, such as estrogens and androgens, in reproductive tissue cancers is clearly outlined. However, one is also reminded that the search for steroid-responsive target genes relevant to tumorigenesis is far from over. Furthermore, we still do not understand how these types of cancers progress into a hormoneindependent growth phase. It is implied that cross-talk between steroid receptors and the growth factor signaling cascades contribute to this process. With an increasing interest in the role of extracellular signaling cascades in nuclear receptor function, one might predict that the next edition would include a full discussion on this subject. The chapters devoted to growth factors and their receptors best illustrate how basic mechanisms are shared by both regulated growth in ontogeny and dysregulated growth in cancer. We are reminded repeatedly by specific genetic examples that neoplasia is truly a developmental program which has lost one or more of its regulatory safeguards. Lohmeyer and Gullick provide a wonderful and comprehensive review on activating mutations of tyrosine kinase receptor pathways that result in various human cancers. Two chapters emphasize how alterations in the tyrosine kinase ErbB-2/Neu/HER2 gene contribute to breast cancer and provide exciting examples of novel therapeutic targets for therapy. Jonsson, Smith, and Harris detail the exquisite new discoveries in Drosophila and mammalian WNT (wingless) pathways and illustrate how information from an invertebrate genetic system converges with mammalian cell biology to provide insight into multiple human diseases. Collectively, this set of reviews on growth factors and cancer demonstrates how the availability of genetic reagents in mice (i.e., gain or loss of function) makes it possible to establish genetic cascades of both organ development and neoplasia in mammals.
In summary, this ambitious and timely undertaking by Dickson and Salomon is well worth having as a reference and addresses issues not currently covered by standard textbooks in the field (i.e., Williams Textbook of Endocrinology or Gilbert’s Developmental Biology textbook). Remarkably, there have been very few concerted efforts to integrate hormone signaling with development and cancer. Given that these fields are advancing rapidly, we predict that this excellent book will only improve with subsequent editions.
Holly A. Ingraham and Gary D. Hammer Departments of Physiology and Medicine University of California, San Francisco San Francisco, California 94143–0444
Relishing Regulation and Receptors Hormones and Signaling, Volume 1 Edited by Bert W. O’Malley et al. San Diego, CA: Academic Press (1998). 364 pp. $69.95
Deciphering the molecular mechanisms that underlie the integration of extracellular and intracellular signals and direct transcriptional responses in development, homeostasis, and transformation has been the focus of intense investigation over the present decade using diverse organisms as models. Contemporary technologies have catalyzed a deluge of information that has rapidly altered models in this area. The challenge to organize and interpret this data presents a particular need for effective reviews. The first volume of Hormones and Signaling, which was edited by O’Malley and an outstanding group of associate editors, represents one approach to this need, offering ten reviews. While some of these chapters are tightly linked to the authors’ major research contributions, others provide broad reviews of more general questions. Four articles deal with aspects of nuclear receptor biology, two with cell death, and the remainder with regulatory events as diverse as response to stress, and fertilization. While there is no particular logic to the chapter organization, several of the reviews are highly complementary. Reading all the chapters dealing with nuclear receptors, followed by those on signaling, might permit the reader an easier access to the general themes. Several chapters deal with aspects of extracellular signaling. The most rewarding is the chapter by Minden and Karin, “The JNK Family of MAP Kinases: Regulation and Function,” reviewing the history of discovery of the Jun cyclohexamide-activated protein kinases and regulation of c-Jun expression and activity, based on specific phosphorylation. The parallels between signaling pathways in yeast regulating cell wall integrity, mating, and osmotic stress, and the corresponding mammalian pathways, provide a useful analogy. Cross-talk between the Raf-1, MEKK-1, and ASK pathways and the roles of PAK1, PAK2, PAK65, Rac, and Cdc42 are particularly
1997). The work on RNA localization does nothing less than offer a new vocabulary for thinking about transcription as it applies to cell polarity. These experiments demonstrate that the advanced microscopy techniques now available will contribute as much to our understanding of polarity as the molecular analyses of the last decade. Frank Solomon Massachusetts Institute of Technology Center for Cancer Research Cambridge, Massachusetts 02139
Raging Hormones in Development and Cancer Hormones and Growth Factors in Development and Neoplasia By Robert B. Dickson and David S. Salomon New York: Wiley (1998). 461 pp. $125.00 Have you ever wondered how a witch’s brew can transform a handsome prince into a toad or, as a colleague recently pleaded, how an angelic twelve-year-old daughter suddenly becomes a “hormonally challenged” teenager? Indirectly, Robert Dickson and David Salomon take on these questions in their recent book Hormones and Growth Factors in Development and Neoplasia. Specifically, they ask how signaling molecules such as hormones and growth factors lead to profound changes during development and ponder why these same molecules are implicated in prevalent cancers, such a breast, ovary, prostate, and others. In doing so they have provided a unique book that integrates our current understanding of hormone/growth factor signaling with invertebrate and vertebrate model systems in development and disease. While there are some obvious shortcomings in this initial undertaking to integrate very diverse fields, the editors have compiled an excellent set of chapters, some of which are especially relevant for those working in the area of reproduction. Indeed, the editors chose deliberately to emphasize reproduction because of the prominent role of hormones and growth factors in both pre- and postnatal reproductive development and because today human cancers are so prevalent in reproductive tissues. The contents of this book are broken into four sections. The first restricts its discussion to hormones and growth factors in invertebrate model systems; as a whole this section is extremely well written and is probably the best aspect of the book. The second section follows by detailing how growth factors influence mammalian development. In the third and more specialized section, postnatal developmental processes are discussed, in particular, reproductive tract and mammary gland development. The fourth and largest section provides a series of exciting perspectives on the known roles of hormones and growth factor signaling in tumor progression. For the uninitiated who might be drawn to
this book by its snappy cover and title, an overview and introductory chapter won’t be found. Even sophisticated readers might have benefited from some simple schematics summarizing the various signaling pathways discussed in the subsequent chapters. A brief overview of hormone action outlining the classes of growth factors, polypeptide hormones, steroid hormones, and their receptors would have been appreciated. Nonetheless, despite this omission, many of the chapters do provide a cogent and concise introduction in their particular area of interest. As with most multi-authored books, some chapters are superb while others are not—we will highlight those that fall into the former category. The first and, perhaps, one of the best sections of the book offers some illustrative examples of how hormones and growth factors affect invertebrate development. All of these chapters are well organized, well written, and informative. One could speculate that the consistent quality of this section stems from the ability to exploit these powerful genetic systems. For those of us entrenched in mammalian systems, lessons learned from the genetic pathways described for Drosophila and Caenorhabditis elegans prove to be extremely instructive. For example, the chapter by Bier elegantly describes the convergence of two signaling pathways, the tyrosine kinase (EGF-R) and TGF-b pathways, in early neurogenesis and wing vein development in Drosophila. From these two developmental events we learn that both synergy and antagonism occur between the EGF-R and TGF-b pathways. This cell-dependent divergence of shared signaling cascades may contribute to different stages of tumor formation in vertebrates. Segraves provides an outstanding chapter on steroid action in larval molting and metamorphosis in Drosophila. These dramatic developmental processes serve to underscore how one signaling hormone, such as ecdysone, initiates different developmental programs of gene expression in multiple tissues. Indeed, it is this very question that underlies so much of the current scientific inquiry into nuclear receptor function and hormone action. Interestingly, we still do not know the molecular identity of one important component of metamorphosis, the juvenile hormone receptor in Drosophila. Moreover, with the recent discovery of z200 putative orphan nuclear receptors in C. elegans via the genome project, assigning a ligand with its bona fide receptor will continue to pose a serious challenge to those in the steroid/hormone nuclear receptor field. Although many of the chapters describing the mammalian model systems are less refined, genetic studies conducted within the last several years are beginning to provide a more comprehensive picture, at least in mice. The roles of growth factors in early mammalian development are summarized in the chapter by Rappolee, which offers an up-to-date review of all factors known to affect both pre- and postimplantation. An excellent chapter by Yarden and others summarizes current data on the complex network of ligand and receptors in tyrosine kinase signaling. After reading this chapter (which is quite useful for subsequent chapters in the fourth section), it is apparent that much work has yet to be done to break the complex signaling code of this remarkable family of growth factors. Chapters
Book Reviews 477
discussing the role of hormones and growth factors in postnatal development focus primarily on reproductive tract and mammary gland development. Here, these biological systems demonstrate that any cell–cell communication (i.e., autocrine and paracrine signaling) can be considered to be hormone action. This broader definition is nicely illustrated in Cunha’s chapter on reproductive tract development and in the two chapters describing prolactin signaling in mammary gland development by Hennighausen and Vonderhaar. In considering how hormones influence reproductive development, a relevant topic that was not formally covered in this section, but was mentioned, is the subject of endocrine disrupters. There is growing concern (and controversy) about the potential of environmental agents, mimicking hormones, to cause developmental defects in humans and wildlife. Since hormone responsiveness in the embryo may be fundamentally different from that in the adult (reviewed in Limbard, L., and Taylor, P. Cell, 157–163, 1998), endocrine disrupters could potentially provide a tool to dissect hormone signaling in development and neoplasia from signaling in normal adult physiology. Perhaps, the second edition of this book will include a dedicated chapter devoted to this important issue. The final section of this book focuses on current research detailing the roles of sex steroids, peptide hormones, and growth factors in formation and progression of human cancers. In a number of these reviews, the prominent role of steroids, such as estrogens and androgens, in reproductive tissue cancers is clearly outlined. However, one is also reminded that the search for steroid-responsive target genes relevant to tumorigenesis is far from over. Furthermore, we still do not understand how these types of cancers progress into a hormoneindependent growth phase. It is implied that cross-talk between steroid receptors and the growth factor signaling cascades contribute to this process. With an increasing interest in the role of extracellular signaling cascades in nuclear receptor function, one might predict that the next edition would include a full discussion on this subject. The chapters devoted to growth factors and their receptors best illustrate how basic mechanisms are shared by both regulated growth in ontogeny and dysregulated growth in cancer. We are reminded repeatedly by specific genetic examples that neoplasia is truly a developmental program which has lost one or more of its regulatory safeguards. Lohmeyer and Gullick provide a wonderful and comprehensive review on activating mutations of tyrosine kinase receptor pathways that result in various human cancers. Two chapters emphasize how alterations in the tyrosine kinase ErbB-2/Neu/HER2 gene contribute to breast cancer and provide exciting examples of novel therapeutic targets for therapy. Jonsson, Smith, and Harris detail the exquisite new discoveries in Drosophila and mammalian WNT (wingless) pathways and illustrate how information from an invertebrate genetic system converges with mammalian cell biology to provide insight into multiple human diseases. Collectively, this set of reviews on growth factors and cancer demonstrates how the availability of genetic reagents in mice (i.e., gain or loss of function) makes it possible to establish genetic cascades of both organ development and neoplasia in mammals.
In summary, this ambitious and timely undertaking by Dickson and Salomon is well worth having as a reference and addresses issues not currently covered by standard textbooks in the field (i.e., Williams Textbook of Endocrinology or Gilbert’s Developmental Biology textbook). Remarkably, there have been very few concerted efforts to integrate hormone signaling with development and cancer. Given that these fields are advancing rapidly, we predict that this excellent book will only improve with subsequent editions.
Holly A. Ingraham and Gary D. Hammer Departments of Physiology and Medicine University of California, San Francisco San Francisco, California 94143–0444
Relishing Regulation and Receptors Hormones and Signaling, Volume 1 Edited by Bert W. O’Malley et al. San Diego, CA: Academic Press (1998). 364 pp. $69.95
Deciphering the molecular mechanisms that underlie the integration of extracellular and intracellular signals and direct transcriptional responses in development, homeostasis, and transformation has been the focus of intense investigation over the present decade using diverse organisms as models. Contemporary technologies have catalyzed a deluge of information that has rapidly altered models in this area. The challenge to organize and interpret this data presents a particular need for effective reviews. The first volume of Hormones and Signaling, which was edited by O’Malley and an outstanding group of associate editors, represents one approach to this need, offering ten reviews. While some of these chapters are tightly linked to the authors’ major research contributions, others provide broad reviews of more general questions. Four articles deal with aspects of nuclear receptor biology, two with cell death, and the remainder with regulatory events as diverse as response to stress, and fertilization. While there is no particular logic to the chapter organization, several of the reviews are highly complementary. Reading all the chapters dealing with nuclear receptors, followed by those on signaling, might permit the reader an easier access to the general themes. Several chapters deal with aspects of extracellular signaling. The most rewarding is the chapter by Minden and Karin, “The JNK Family of MAP Kinases: Regulation and Function,” reviewing the history of discovery of the Jun cyclohexamide-activated protein kinases and regulation of c-Jun expression and activity, based on specific phosphorylation. The parallels between signaling pathways in yeast regulating cell wall integrity, mating, and osmotic stress, and the corresponding mammalian pathways, provide a useful analogy. Cross-talk between the Raf-1, MEKK-1, and ASK pathways and the roles of PAK1, PAK2, PAK65, Rac, and Cdc42 are particularly