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Oncogenes: An introduction to the concept of cancer genes
TIBS 14- May 1989
196
Book Reviews Plant pigments in perspective Plant P i g m e n t s edited by T. W. Goodwin, Academic
Press, 1988. £35.00 (x+362 pages) ISBN0122898478 Chorophylls, carotenoids and flavonoids are the predominant plant pigmerits in nature. Phytochrome, a proteinaceous pigment found in very small amounts, controls many aspects of plant development. The chemical structure of these pigments, how they are synthesized in the plant and what functions they perform, are problems that intrigue us. As a result, every year a large number of research papers are published dealing with plant pigments, A book written on plant pigments therefore has to be periodically revised in order to keep up with constant development of new ideas and technology,
The Chemistry and Biochemistry of Plant Pigments (first Edn 1965; second Edn 1976) has fulfilled this requirement successfully to date. Significant advances (especially in the elucidation of the chemistry and photochemistry o f p h y t o c h r o m e and of several enzymic steps in chlorophyll biosynthesis) have taken place since the last revision of this book. Instead of producing a third edition of the same book, the editor has chosen to produce a new textbook entitled Plant Pigments. The 'current growing points' in plant pigment research were identified and the advances made in these areas since 1976 summarized by leading experts. There are seven chapters, written by nine authors, The chapter on chlorophylls (by W. Rudiger and S. Schoch) is an exhaustive review covering nearly all the papers published on this subject from 1976 to 1987. The biochemistry of chlorophyll synthesis has been treated in great detail and clarity and the article is highly recommended to everyone interested in thistopic. For chlorophyll biosynthesis in higher plants many enzymes and reactions are still very poorly characterized andwe depend on results from bacteria or animal tissues to infer their function. Some of the postulated enzymes and biosynthetic steps may turn out to be unusual and
exciting. This chapter should create considerable interest to initiate more research on the difficult isolation and molecular characterization of these enzymes, The analysis and biosynthesis of carotenoids are covered in two separate chapters. 'Analysis of Carotenoids' (T. Goodwin and G. Britton) presents in detail the HPLC technique for purlfication and quantitation of these pigments. A full complement of physical methods useful in the identification of carotenoids (e.g. NMR, CD, ORD, MS, IR and resonance Raman spectroscopy) are discussed. Beginners in this field will find this section very useful, The chapter on biosynthesis of carotenoids (G. Britton) is similar to the one written by the same author in the previous book. It discusses the recent studies on the formation of phytoene, desaturation and cyclization, and clarities some of the issues raised previously, The chapter entitled 'The Function of Pigments in Chloroplasts' (R. Cogdell) presents the organization of photosystems, dealing mainly with the chlorophyll-binding proteins and their function. In addition, the significant advances made on the bacterial reaction center and the phycobilisome are presented. Several recent publications on chlorophyll-binding proteins are not considered, but this chapter brings out the present state of understanding of chlorophyll-binding proteins and their function in photosynthesis, The significant advances made on blue-light photoreception are covered by W. Rau in the chapter entitled
'Function of Carotenoids other than in Photosynthesis'. The number of research papers published on blue-light photoreception in the last ten years only slightly exceeds the number of reviews written on this subject. M o s t o f the functions of the carotenoid pigmerits discussed in this chapter appeared in greater detail in the previousbook. Phytochrome controls a large humbet of developmental and metabolic processes in the green plant. A number of reviews dealing with physiological effects caused by phytochrome are available. The present review, however, is different and refreshing. Written by G. Whitelam and H. Smith, it gives a comprehensive coverage of phytochrome in terms of the protein molecule, covering its chemistry, photochemistry, biosynthesis and dogradation. In the chapter entitled 'Flavonoids: Recent Advances' J. B. Harborne reviews the progress made since 1976, emphasizing the analytical methods, chemistry of anthocyanins and the enzymes involved in flavonoid biosynthesis and modification. It is unfortunate that the molecular biological studies pertaining to flavonoid metabolism are notincludedinthisreview. Plant pigments serves to update its predecessor, Chemistry and Biochemistrv of Plant Pigments', in several selccted areas. It is short compared to the previous one (which ranto 1243pages), but is well written and can be recommended for university students interested in biochemistry and plant pigments, c. GAMINIKANNANGARA D~TmrtmentofPhysiology, CarlsbergLahoratoo, ' GarnleCarlsbergVejlO, ('openhagen, Denmark.
An ideal overview O n c o g e n e s : A n I n t r o d u c t i o n to the
Concept of Cancer Genes edited by K. B. Burcle, E. T. Liu and J . W . Larrick, Springer-Verlag, 1988.
DM54.00 (vii+3OOpages) ISBN 0 387 96423 1 The molecular biology of human cancer has its roots in the analysis of avian retroviruses and today's physicians, in particular, need to be re-
minded that even ten years ago there was much scepticism that chicken cancer research would have any impact on understanding human malignancy. The discovery of oncogenes and subsequently proto-oncogenes is yet another example, however, of how any research in basic biology may ultimately shed light on human biology and disease. The realization for most that this really was the right place to be in cancer research occurred with the
TIBS 1 4 - May 1989 publication of experiments carried out in Boston by the groups of Weinberg and Cooper. They utilized the D N A transfection assay and found evidence for an oncogene in a human tumor cell line. If an oncogene could be detected in one cell line then why no Lin others and, since 1979, n u m e r o u s l a b o r a t o r i e s all over the world have rooked at thousands of cell lines a:ad t u m o r biopsies using this assay, Not surprisingly an increased understanding of the genetic processes involved in malignancy has coincided with the increasing sophistication of techniques of molecular biology. This has culminated in the completion of o n e o f t h e most satisfying anti demanding exercises possible in molecular and cellular biology; namely, extending cytological observations of a specific deletion on chromosome 13 in familial retinoblastoma through to cloning the retinoblastoma recessive oncogene, Unfortunately, the rapid progress in identifying new oncogenes, l:,oth dominant and recessive, has far outstripped any understanding of the biochemical and biological properties of the proteins they encode, and if one aspect of the last 20 years has been frustrating it is that we still do not know the biochemical basis by which ~Lny oncoprotein transforms a cell. This is particularly embarrassing for those working on the oldest (src) or the most topical (ras) oncogenes, only confirming that biochemistry is much harder than molecular biology. Oncogenes." An Introduction to the Concept of Cancer Genes, is designed to help the non-specialist physician or scientist understand recent developments in the molecular biology of cancer. This is not a straightforward task and this book falls into the same trap as many others of presenting too much information and too many facts for the stated audience. Having said that, I think the book will be very helpful to a different audience:, namely students (physicians or scientists) wishingtoenterthisfieldofresearch, The book itself begins with a very worthwhile purpose - to educate the non-specialist in the techniques of molecular biology. However, I am not sure that 30 pages in a book on on,zogenes is the place. Being familiar with these techniques it is difficult to assess how useful this will be to different groups, but readers with no molecular biology courses under their belt are unlikely to get very much out of this whistle-stop tour and I can only guess that it was
197 included as a refresher course for those who once knew. From then on, the book covers all areas of modern molecular biology of cancer to varying degrees. I could find no relevant area that had been omitted and most chapters end with over 50 references including titles. For a book containing large amounts of data and specific experimeats, I found it annoying that references were not given at relevant positions in the text. The book does not contain many errors though the enigm a t i c ' E m a x ' present in the headings of several of the tables and the spectacularly confusing Figure 8.3 deserve some comment, Chapters 3 and 4 go into D N A and R N A t u m o r viruses in some detail, They give a nice flavour of the variety of viral agents capable of inducing cancer and the ways in which they might act, but again this is couched in some very detailed descriptions of particular experiments and 1 am sure this would be confusing to the uninitiated, Chapters 5 and 6 lead on from viral oncogenes to cover cellular protooncogenes and in particular focusing on those which have been shown to bc affected in human cancer, disappointingly still a small fraction of the total, The next five chapters look in more detail at individual oncogenes and we learn about the variety of biochemical properties that can be associated with oncoproteins. I thought the final chap-
ters were particularly useful, introducing and discussing some very clinically relevant questions. First what do oncogenes do in vivo and the use of transgenic mice is having a growing impact on the way this problem is investigated. It is also relevant to ask at this time what are the potential diagnostic and therapeutic implications of 20 years of oncogene research. These are discussed in two chapters on what might be, though so far there are few tangible examples to quote from the cancer field. All in all, this is a useful survey of the field of oncogene research which now impinges on so many other areas of biochemical and biological investigation: growth, differentiation and development to name a few. Students in any of these areas would need to be aware of most of what is in this book. I would certainly r e c o m m e n d it to new graduate students coming into this field. As for physicians- this is always a difficult one - the book is not 'an easy r e a d ' b u t for physicianswhoare k e e n t o do modern cancer research and to have a good foundation in molecular biology, this book is an ideal overview of thc whole area and should impart a feeling for what they are letting themselves in for. ALAN HALL Tile Institute of Cancer Research, Royal Cancer Hospital, Chester Beatty Laboratories, Fulham Road.LondonSW3 6JB, UK.
We know a great deal and understand Receptor Biochemistry and M e t h o d o l o g y , Vol. 12: Insulin R e c e p t o r s , P a r t A : M e t h o d s for t h e Study of Structure and Function; a n d P a r t B: Clinical A s s e s s m e n t , Biological Responses and C o m p a r i s o n to the I G F - 1 R e c e p t o r edited by C. R. Kahn and L. C. Harrison, Alan R. Liss, 1988. $96.00 (xiii+304 pages) 1SBN 0 8451 3798 0 (PartA)/$70.00 (xiii+220pages)ISBN 0 8451 3799 9 (Part B) When I first became interested in insulin I came across a quotation from a then recent (1968) review by Ira Wool in 'Recent Progress in H o r m o n e Research', to the effect t h a t . . . 'about insulin mechanism of action it may truthfully be said that we know a great deal and understand nothing'. Twenty-
nothing
one years on we know very much more and are beginning to understand a little, but the contents of these volumes on insulin receptors are testimony to the continuing ability of insulin to fascinate a large body of researchers while refusing to give up the last of its secrets. These books cover topics and techniques undreamt of in 1968, when the idea was only just emerging that the primary site of interaction of insulin with cells was the plasma m e m b r a n e , perhaps via a specific receptor on the cell surface which mediated the diverse intracellular effects. The insulin receptot at least has come a long way since then, and there is much we now know about its distribution, structure and activity. However, the central issue of the signalling mechanisms by which the insulin-receptor complex regulates intracellular enzymes is unresolved,
196
Book Reviews Plant pigments in perspective Plant P i g m e n t s edited by T. W. Goodwin, Academic
Press, 1988. £35.00 (x+362 pages) ISBN0122898478 Chorophylls, carotenoids and flavonoids are the predominant plant pigmerits in nature. Phytochrome, a proteinaceous pigment found in very small amounts, controls many aspects of plant development. The chemical structure of these pigments, how they are synthesized in the plant and what functions they perform, are problems that intrigue us. As a result, every year a large number of research papers are published dealing with plant pigments, A book written on plant pigments therefore has to be periodically revised in order to keep up with constant development of new ideas and technology,
The Chemistry and Biochemistry of Plant Pigments (first Edn 1965; second Edn 1976) has fulfilled this requirement successfully to date. Significant advances (especially in the elucidation of the chemistry and photochemistry o f p h y t o c h r o m e and of several enzymic steps in chlorophyll biosynthesis) have taken place since the last revision of this book. Instead of producing a third edition of the same book, the editor has chosen to produce a new textbook entitled Plant Pigments. The 'current growing points' in plant pigment research were identified and the advances made in these areas since 1976 summarized by leading experts. There are seven chapters, written by nine authors, The chapter on chlorophylls (by W. Rudiger and S. Schoch) is an exhaustive review covering nearly all the papers published on this subject from 1976 to 1987. The biochemistry of chlorophyll synthesis has been treated in great detail and clarity and the article is highly recommended to everyone interested in thistopic. For chlorophyll biosynthesis in higher plants many enzymes and reactions are still very poorly characterized andwe depend on results from bacteria or animal tissues to infer their function. Some of the postulated enzymes and biosynthetic steps may turn out to be unusual and
exciting. This chapter should create considerable interest to initiate more research on the difficult isolation and molecular characterization of these enzymes, The analysis and biosynthesis of carotenoids are covered in two separate chapters. 'Analysis of Carotenoids' (T. Goodwin and G. Britton) presents in detail the HPLC technique for purlfication and quantitation of these pigments. A full complement of physical methods useful in the identification of carotenoids (e.g. NMR, CD, ORD, MS, IR and resonance Raman spectroscopy) are discussed. Beginners in this field will find this section very useful, The chapter on biosynthesis of carotenoids (G. Britton) is similar to the one written by the same author in the previous book. It discusses the recent studies on the formation of phytoene, desaturation and cyclization, and clarities some of the issues raised previously, The chapter entitled 'The Function of Pigments in Chloroplasts' (R. Cogdell) presents the organization of photosystems, dealing mainly with the chlorophyll-binding proteins and their function. In addition, the significant advances made on the bacterial reaction center and the phycobilisome are presented. Several recent publications on chlorophyll-binding proteins are not considered, but this chapter brings out the present state of understanding of chlorophyll-binding proteins and their function in photosynthesis, The significant advances made on blue-light photoreception are covered by W. Rau in the chapter entitled
'Function of Carotenoids other than in Photosynthesis'. The number of research papers published on blue-light photoreception in the last ten years only slightly exceeds the number of reviews written on this subject. M o s t o f the functions of the carotenoid pigmerits discussed in this chapter appeared in greater detail in the previousbook. Phytochrome controls a large humbet of developmental and metabolic processes in the green plant. A number of reviews dealing with physiological effects caused by phytochrome are available. The present review, however, is different and refreshing. Written by G. Whitelam and H. Smith, it gives a comprehensive coverage of phytochrome in terms of the protein molecule, covering its chemistry, photochemistry, biosynthesis and dogradation. In the chapter entitled 'Flavonoids: Recent Advances' J. B. Harborne reviews the progress made since 1976, emphasizing the analytical methods, chemistry of anthocyanins and the enzymes involved in flavonoid biosynthesis and modification. It is unfortunate that the molecular biological studies pertaining to flavonoid metabolism are notincludedinthisreview. Plant pigments serves to update its predecessor, Chemistry and Biochemistrv of Plant Pigments', in several selccted areas. It is short compared to the previous one (which ranto 1243pages), but is well written and can be recommended for university students interested in biochemistry and plant pigments, c. GAMINIKANNANGARA D~TmrtmentofPhysiology, CarlsbergLahoratoo, ' GarnleCarlsbergVejlO, ('openhagen, Denmark.
An ideal overview O n c o g e n e s : A n I n t r o d u c t i o n to the
Concept of Cancer Genes edited by K. B. Burcle, E. T. Liu and J . W . Larrick, Springer-Verlag, 1988.
DM54.00 (vii+3OOpages) ISBN 0 387 96423 1 The molecular biology of human cancer has its roots in the analysis of avian retroviruses and today's physicians, in particular, need to be re-
minded that even ten years ago there was much scepticism that chicken cancer research would have any impact on understanding human malignancy. The discovery of oncogenes and subsequently proto-oncogenes is yet another example, however, of how any research in basic biology may ultimately shed light on human biology and disease. The realization for most that this really was the right place to be in cancer research occurred with the
TIBS 1 4 - May 1989 publication of experiments carried out in Boston by the groups of Weinberg and Cooper. They utilized the D N A transfection assay and found evidence for an oncogene in a human tumor cell line. If an oncogene could be detected in one cell line then why no Lin others and, since 1979, n u m e r o u s l a b o r a t o r i e s all over the world have rooked at thousands of cell lines a:ad t u m o r biopsies using this assay, Not surprisingly an increased understanding of the genetic processes involved in malignancy has coincided with the increasing sophistication of techniques of molecular biology. This has culminated in the completion of o n e o f t h e most satisfying anti demanding exercises possible in molecular and cellular biology; namely, extending cytological observations of a specific deletion on chromosome 13 in familial retinoblastoma through to cloning the retinoblastoma recessive oncogene, Unfortunately, the rapid progress in identifying new oncogenes, l:,oth dominant and recessive, has far outstripped any understanding of the biochemical and biological properties of the proteins they encode, and if one aspect of the last 20 years has been frustrating it is that we still do not know the biochemical basis by which ~Lny oncoprotein transforms a cell. This is particularly embarrassing for those working on the oldest (src) or the most topical (ras) oncogenes, only confirming that biochemistry is much harder than molecular biology. Oncogenes." An Introduction to the Concept of Cancer Genes, is designed to help the non-specialist physician or scientist understand recent developments in the molecular biology of cancer. This is not a straightforward task and this book falls into the same trap as many others of presenting too much information and too many facts for the stated audience. Having said that, I think the book will be very helpful to a different audience:, namely students (physicians or scientists) wishingtoenterthisfieldofresearch, The book itself begins with a very worthwhile purpose - to educate the non-specialist in the techniques of molecular biology. However, I am not sure that 30 pages in a book on on,zogenes is the place. Being familiar with these techniques it is difficult to assess how useful this will be to different groups, but readers with no molecular biology courses under their belt are unlikely to get very much out of this whistle-stop tour and I can only guess that it was
197 included as a refresher course for those who once knew. From then on, the book covers all areas of modern molecular biology of cancer to varying degrees. I could find no relevant area that had been omitted and most chapters end with over 50 references including titles. For a book containing large amounts of data and specific experimeats, I found it annoying that references were not given at relevant positions in the text. The book does not contain many errors though the enigm a t i c ' E m a x ' present in the headings of several of the tables and the spectacularly confusing Figure 8.3 deserve some comment, Chapters 3 and 4 go into D N A and R N A t u m o r viruses in some detail, They give a nice flavour of the variety of viral agents capable of inducing cancer and the ways in which they might act, but again this is couched in some very detailed descriptions of particular experiments and 1 am sure this would be confusing to the uninitiated, Chapters 5 and 6 lead on from viral oncogenes to cover cellular protooncogenes and in particular focusing on those which have been shown to bc affected in human cancer, disappointingly still a small fraction of the total, The next five chapters look in more detail at individual oncogenes and we learn about the variety of biochemical properties that can be associated with oncoproteins. I thought the final chap-
ters were particularly useful, introducing and discussing some very clinically relevant questions. First what do oncogenes do in vivo and the use of transgenic mice is having a growing impact on the way this problem is investigated. It is also relevant to ask at this time what are the potential diagnostic and therapeutic implications of 20 years of oncogene research. These are discussed in two chapters on what might be, though so far there are few tangible examples to quote from the cancer field. All in all, this is a useful survey of the field of oncogene research which now impinges on so many other areas of biochemical and biological investigation: growth, differentiation and development to name a few. Students in any of these areas would need to be aware of most of what is in this book. I would certainly r e c o m m e n d it to new graduate students coming into this field. As for physicians- this is always a difficult one - the book is not 'an easy r e a d ' b u t for physicianswhoare k e e n t o do modern cancer research and to have a good foundation in molecular biology, this book is an ideal overview of thc whole area and should impart a feeling for what they are letting themselves in for. ALAN HALL Tile Institute of Cancer Research, Royal Cancer Hospital, Chester Beatty Laboratories, Fulham Road.LondonSW3 6JB, UK.
We know a great deal and understand Receptor Biochemistry and M e t h o d o l o g y , Vol. 12: Insulin R e c e p t o r s , P a r t A : M e t h o d s for t h e Study of Structure and Function; a n d P a r t B: Clinical A s s e s s m e n t , Biological Responses and C o m p a r i s o n to the I G F - 1 R e c e p t o r edited by C. R. Kahn and L. C. Harrison, Alan R. Liss, 1988. $96.00 (xiii+304 pages) 1SBN 0 8451 3798 0 (PartA)/$70.00 (xiii+220pages)ISBN 0 8451 3799 9 (Part B) When I first became interested in insulin I came across a quotation from a then recent (1968) review by Ira Wool in 'Recent Progress in H o r m o n e Research', to the effect t h a t . . . 'about insulin mechanism of action it may truthfully be said that we know a great deal and understand nothing'. Twenty-
nothing
one years on we know very much more and are beginning to understand a little, but the contents of these volumes on insulin receptors are testimony to the continuing ability of insulin to fascinate a large body of researchers while refusing to give up the last of its secrets. These books cover topics and techniques undreamt of in 1968, when the idea was only just emerging that the primary site of interaction of insulin with cells was the plasma m e m b r a n e , perhaps via a specific receptor on the cell surface which mediated the diverse intracellular effects. The insulin receptot at least has come a long way since then, and there is much we now know about its distribution, structure and activity. However, the central issue of the signalling mechanisms by which the insulin-receptor complex regulates intracellular enzymes is unresolved,