| 书目名称 | Oncogenes and Growth Control | | 编辑 | Patricia Kahn,Thomas Graf | | 视频video | | | 图书封面 |  | | 描述 | How is growth controlled in normal cells? How are the growth control mechanisms perturbed in cancer cells? This book provides an up-to-date description of research aimed at resolving these questions. It is organized into four sections, each containing a series of short reviews written by experts in the field. The general headings are: growth factors, receptors, and related oncogenes: transduction of mitogenic signals and .ras. oncogenes; nuclear oncogenes and regulation of gene expression; and multiple steps involved in malignant transformation. The articles emphasize concepts rather than detailed facts and are intended not only for specialists in the field but also for interested readers, such as physicians and advanced students, who wish to stay abreast of developments in one of the most exciting fields in current biomedical research. | | 出版日期 | Book 1986 | | 关键词 | ATP; Activation; Colon; DNA; Interleukin-2; Viruses; gene expression; interferon; regulation; transcription; t | | 版次 | 1 | | doi | https://doi.org/10.1007/978-3-642-73325-3 | | isbn_softcover | 978-3-540-18760-8 | | isbn_ebook | 978-3-642-73325-3 | | copyright | Springer-Verlag Berlin Heidelberg 1986 |
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Front Matter |
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Abstract
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Introduction |
Patricia Kahn,Thomas Graf |
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Abstract
In recent years there has been a virtual explosion in our understanding of the mechanisms which regulate vertebrate cell proliferation. This applies both to normal cells, in which growth is tightly controlled, as well as to cancer cells, which divide in an uncontrolled fashion. Molecular and biochemical studies have led to the identification of a number of genes whose products are involved in regulating normal cell growth. In addition, many genes which are capable of inducing a transformed phenotype have been identified. Perhaps most important in fueling the remarkable progress of the past few years was the demonstration of something which was believed by many, but for a long time remained speculative: that these two groups of genes are in fact largely one and the same. This realization has been tremendously catalytic for both areas of research, and is the central concept around which this book is organized.
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Abstract
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The Expression of Growth Factors and Growth Factor Receptors During Mouse Embryogenesis |
Aya Jakobovits |
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Abstract
Elucidation of molecular mechanisms underlying embryonic growth control is a key step to understanding embryonic development, as well as the regulation of cellular proliferation and its impairment in malignancy. Since extensive proliferation and differentiation take place during development, it seems likely that growth factors have a major role in embryogenesis. Identification of specific growth factors involved in embryonic development and their characterization is a difficult task because the events that occur at each developmental step are complex and the quantities of embryonic material available are limited. In the mouse, for example, the first 3 days after fertilization are devoted primarily to continuous multiplication. During the next 2 days, the first two differentiation steps take place to form the layers which will give rise to the fetus and to extra-embryonic structures (see Fig. 1). After implantation, at about day 7 of gestation, gastrulation begins, followed by major morphogenetic and organogenetic processes during the next 5 days. The remainder of the 20-day gestational period is devoted primarily to terminal differentiation and enlargement of the fetus. Therefore,
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A Role for Proto-Oncogenes in Differentiation? |
Erwin F. Wagner,Rolf Müller |
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Abstract
Ever since the discovery of proto-oncogene products in the normal cell, their biological role and molecular function have been of major interest in molecular and cellular biology. To date more than 30 different c-. genes are known which encode proteins localized in the nucleus or cytoplasm, are associated with the plasma membrane or even secreted (see Table 1). It has been presumed from the outset that proto-oncogenes play a role in growth control, mainly because of their potential to induce uncontrolled cell proliferation. This notion is now strongly supported by evidence that the products of several proto-oncogenes are either growth factors or growth-factor receptors (see Hunter, Sherr and Stanley, Heldin, Beug et al., all this Vol.).
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Tissue-Specific Expression and Possible Functions of pp60, |
Larry R. Rohrschneider |
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Abstract
Although some remarkable progress has been made in identifying the function of a few proto-oncogene products such as c-., c-., c-. (see Wagner and Müller; Beug et al.; Sherr and Stanley; Heldin and Westermark, all this Vol.), the function of the c-. protein pp60. has remained an enigma despite the fact that it was the very first proto-oncogene product identified (Collett et al. 1978). The difficulty in studying pp60. is that it occurs at a very low abundance and that it is not easily accessible to the investigator since it is neither secreted nor located at the cell surface (as are the proto-oncogene products listed above). Nevertheless, several analyses of pp60. expression in various tissues and stages of embryogenesis have recently been carried out, and the results promise to shed new light on the regulation of cell growth and differentiation. In the present review, I discuss the significance of these findings for a functional role of the c-. gene product.
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Abstract
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The Granulocyte-Macrophage Colony-Stimulating Factors |
Nicholas M. Gough |
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Abstract
Haemopoiesis is the process whereby a small population of multipotential stem cells continuously gives rise to a large number of mature blood cells which comprise eight distinct cellular lineages. In normal health, the circulating levels of mature cells are remarkably invariant, suggesting that their production is tightly regulated. However, the haemopoietic system is also flexible, allowing fluctuations in the levels of various cell types to meet emergency situations such as blood loss, infection or reduced oxygen tension. Some of the mechanisms controlling haemopoiesis, particularly those concerned with stem cell populations, appear to involve contact between haemopoietic cells and other cells in the micro-environment at the sites of blood cell formation (e.g. Allen 1981). However, the ability to grow colonies of mature haemopoietic cells from single progenitor cells in semi-solid culture systems has also implicated a number of soluble glycoprotein growth factors. These factors, known as colony-stimulating factors (CSFs), have been shown in vitro to stimulate the proliferation, differentiation and functional activation of cells within different haemopoietic lineages (Metcalf 1984
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Role of PDGF-Like Growth Factors in Autocrine Stimulation of Growth of Normal and Transformed Cells |
Carl-Henrik Heldin,Bengt Westermark |
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Abstract
The normal cellular homologs of several retroviral oncogenes have recently been identified as structural genes for proteins which are proven or thought to play a role in mitogenesis. It is therefore likely that the viral oncogene products stimulate uncontrolled cell proliferation by subverting the mitogenic pathway at key regulatory points. An indication that similar mechanisms may operate in nonviral cell transformation comes from the old observation that cell lines established from malignant tumors grow more or less independently of exogenously added growth factors. One possibility, which is supported by recent experimental data, is that transformed cells may produce growth factors that stimulate their own growth in an autocrine manner. This review focuses on platelet-derived growth factor (PDGF) and related factors and their possible role in autocrine and paracrine mechanisms in both normal and transformed cells.
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Transforming Growth Factor-, |
Harold L. Moses,Edward B. Leof |
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Abstract
Transforming growth factor, type . (TGF-.) was first described by its ability to stimulate mouse embryo-derived AKR-2B cells (Moses et al. 1981) and rat NRK cells to grow in soft agar (Roberts et al. 1981). (The latter cells also required the addition of epidermal growth factor, EGF.) Subsequent studies have shown that TGF-. functions as a growth stimulator only for certain fibroblastic cells, possibly through an indirect mechanism involving the induction of endogenous growth-factor synthesis resulting in autocrine growth (Leof et al. 1986). In fact, TGF-. is a growth inhibitor for most cell types tested (Moses et al. 1985a and unpublished observations). Its growth-inhibitory properties, or those of a closely related molecule, were described by Holley and co-workers several years before its growth-stimulatory effects were discovered (Holley et al. 1978; Tucker et al. 1984a). This review discusses the possible mechanism of growth stimulation and growth inhibition by TGF-. and the possible role of this factor in neoplastic transformation.
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Transforming Growth Factor-, |
Rik Derynck |
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Abstract
Transforming growth factor-. (TGF-.) was first detected in the culture medium of certain retrovirus-transformed cell lines as an activity which binds to the receptor for epidermal growth factor (EGF) and thereby inhibits the binding of EGF. Subsequent examination showed that this factor is made by many other transformed cell lines but not by adult normal cells in culture (Todaro et al. 1985). Addition of sarcoma growth factor, as it was first called, to rat fibroblasts of the NRK cell line reversibly induced profound morphological changes and colony-forming ability in soft agar (De Larco and Todaro 1978; Todaro et al. 1985). The capacity of this factor to confer a transformed phenotype upon NRK cells, together with the fact that it is synthesized by transformed cells, led to the name transforming growth factor.
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The Physiology of Epidermal Growth Factor |
Graham Carpenter,Linda Goodman,Lynn Shaver |
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Abstract
Epidermal growth factor (EGF), a small polypeptide of 53 amino acid residues and a molecular mass of approximately 6000 daltons, was identified and isolated nearly 25 years ago (Cohen 1962) and is presently the best characterized epithelial cell mitogen. Although a great deal is known about the structure of both EGF and its receptor, including the primary sequences, several important questions remain unanswered. First, what is the physiological function of EGF? Does it play a role in epithelial cell renewal, which in the human body requires a constantly high rate of cell proliferation (approximately 4×10. cell divisions per second)? Second, by what mechanism does EGF induce cell proliferation? Third, does EGF play a role in the induction and/or maintenance of malignant transformation? The discoveries that many types of malignant cells produce EGF-related proteins (transforming growth factor-.; TGF-.) which have the capacity to induce certain transformed phenotypes (see Derynck, this Vol.) and that molecules related to the EGF receptor can function as oncogenes (v.) suggest that parts of the EGF mechanism may have a role in oncogenesis. The importance of understanding this role is u
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Structural Relationships Between Growth Factor Precursors and Cell Surface Receptors |
Suzanne Pfeffer,Axel Ullrich |
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Abstract
Analysis of the DNA-derived amino acid sequences of several growth factor precursors has revealed the presence of hydrophobic sequences possessing all the characteristics of membrane-spanning domains found in most cell surface receptors. This class of proteins includes the precursors for epidermal growth factor (EGF), transforming growth factor . (TGF-.),and vaccinia virus p19 (pl9vacc). The presence of potential transmembrane domains in these growth factor precursors offers new insight into the evolution of growth factors and their cell surface receptors. The subsequent finding that the EGF precursor shares extensive homology with the low density lipoprotein (LDL) receptor and may not be processed in certain tissues has led to the notion that the EGF precursor may play a dual role as a precursor for a secreted growth factor and, in its unprocessed form, as a cell surface receptor of unknown biological function. Additional distinctive structural features shared by growth factor precursors and growth factor receptors point to a common evolutionary origin for these classes of proteins.
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Regulation of Cell Growth by the EGF Receptor |
Joseph Schlessinger |
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Abstract
Epidermal growth factor (EGF) is a small protein of 53 amino acids which acts as a mitogen for various cell types in vitro and in vivo (Carpenter and Cohen 1979 and Carpenter et al., this Vol.). Several lines of evidence suggest that the receptor for this factor can also play a role in the uncontrolled proliferation characteristic of neoplastic cells. First, the . oncogene of avian erythroblastosis virus encodes a truncated EGF receptor (Downward et al. 1984) and we recently proposed that the . protein transforms by functioning as an activated growth factor receptor (see also article by Beug et al.). Second, various animal and human tumor cells produce a growth factor called transforming growth factor-. (TGF-.; Todaro et al. 1980 and article by Derynck). This growth factor is highly related to EGF; both factors bind to the EGF receptor with similar affinities and induce the proliferation of cells bearing the EGF receptor. It has been suggested that TGF-. plays a role in oncogenesis by inducing autocrine growth (Todaro et al. 1980). Finally, the EGF receptor gene is amplified and rearranged in a significant proportion of human brain tumors of glial origin (Libermann et al. 1985). Th
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Mutational Analysis of v-, Oncogene Function |
Hartmut Beug,Michael J. Hayman,Björn Vennström |
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Abstract
The v. oncogene is contained in two strains of avian erythroblastosis virus (AEV) and encodes their capacity to cause erythroleukemia and sarcomas in chickens. Recent work has revealed that the v. gene product represents a truncated and mutated version of the EGF receptor (Downward et al. 1984; Ullrich et al. 1984). This finding was surprising in light of the fact that AEV in hematopoietic cell lineages selectively transforms erythroid cells, which are not known to express the epidermal growth factor (EGF) receptor. Sequence comparisons showed that v. is also related to the family of oncogenes encoding tyrosine kinases (Yamamoto et al. 1983).
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The c-, Proto-Oncogene and the CSF-1 Receptor |
Charles J. Sherr,E. Richard Stanley |
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Abstract
Cell surface receptors have been traditionally defined through their specific interaction with purified ligands, but the study of oncogene-coded tyrosine kinases and their proto-oncogene homologs has presented the reciprocal problem — namely, can ligands for putative receptors be identified? The demonstration that the v-. oncogene encodes a truncated form of the epidermal growth factor (EGF) receptor (Downward et al. 1984b) provided the first direct evidence that certain oncogene products could be derived from receptor genes, and underscored the possibility that critical alterations in receptor function might directly contribute to neoplasia. Investigators now suspect that other retroviral oncogenes of the tyrosine kinase gene family (v-., v-., v-./., v-., v-., and v-.), as well as functionally related oncogenes derived from tumor cells (., ., .), could also have arisen from receptor genes. One paradigm involves a member of this gene family, c-., which encodes a product related, and possibly identical, to the receptor for the macrophage colony-stimulating factor, CSF-1 (Sherr et al. 1985).
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Activation of the c-, Gene |
Hidesaburo Hanafusa |
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Abstract
Ever since the demonstration that acutely transforming viruses carry oncogenes derived from cellular genes, the basis for the functional differences between the products of these cellular proto-oncogenes (c-. genes) and their viral counterparts (v-. genes) has been an important issue. Comparison of the c-. gene product to that of the v-. gene encoded by the Rous sarcoma virus (RSV) indicated that the two proteins are similar in size and enzyme activity, but quite different in relative abundance. This finding raised the basic question of whether transformation by RSV is due to the mere overproduction of the c-. gene product (as a consequence of placing the gene under the control of viral regulatory elements) or whether qualitative alteration of the coding sequences is involved in “activating” the transformation potential of c-.. Early biological studies demonstrated the rescue of transforming sarcoma viruses from chickens infected with RSV mutants which contained deletions in the . gene, indicating that c-. sequences can replace v-. sequences in RSV to restore transforming activity (Hanafusa et al. 1977). However, since this rescue occurred via homologous recombination between the r
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Normal and Transforming N-Terminal Variants of c-, |
Yinon Ben-Neriah,David Baltimore |
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Abstract
. was first described as the oncogene contained in Abelson murine leukemia virus (A-MuLV), a virus that transforms both lymphocytes and fibroblast lines. The v-. gene product has a protein tyrosine kinase activity which is essential for the transforming capacity of the virus (Prywes et al. 1983). The normal cellular counterpart, the c-. proto-oncogene, also encodes a protein with tyrosine kinase activity (Konopka and Witte 1985; Ben-Neriah et al. 1986a). In addition to capture by retroviruses, c-. can be activated by chromosomal translocations, such as in human chronic myeloid leukemia. In this review we discuss the structure of the c-. gene, the various transcripts it expresses, and how it is activated to become an oncogene.
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Transformation by the v-, Oncogene |
Angelika Gebhardt,J. Gordon Foulkes |
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Abstract
The previous chapter by Ben-Neriah and Baltimore described sequences of the v-. gene which are important in cell transformation. In this chapter, we present some thoughts as to the biochemical mechanisms whereby the v-. protein induces the multitude of changes which characterize the transformed phenotype.
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mos |
Donald G. Blair |
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Abstract
The Moloney murine sarcoma virus (Mo-MSV; Moloney 1966), isolated over 20 years ago from a Balb/c rhabdomyosarcoma induced by high multiplicity passage of the Moloney strain of murine leukemia virus (Mo-MuLV), has been one of the most extensively studied retroviral systems. This review focuses on v-.,the sequence responsible for its acute transforming potential, and on its cellular proto-oncogene homolog, c-.. Although the catalog of oncogene-containing retroviruses is large, . and Mo-MSV represent unique members of this community and have unusual and interesting properties. As will become clear, although . is grouped with the tyrosine kinase oncogenes, its structural and functional peculiarities have set it apart from other members of this group and have hampered attempts to understand its normal role and mechanism of action.
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发表于 2025-3-21 16:28:46
