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Transdifferentiation: Flexibility in cell differentiation
TIBS 1 7 -
The commitment enigma Transdifferentiat~on: Flexibility in Cell Differentiation by T. S. Okada, Oxford University Press, 1991. £45100 (x + 238 pages) ISBN 0 19 854281 X A topic that has excited and perplexed biologists for more than a century is the confined but complex topic of transdifferentiation; that is, how cells change their state of differentiated commitment. Professor Okada's research group has worked in this area for many years. Although this compact, hardback monograph reviews numerous examples of this remarkable cellular phenomenon, the treatment of the subject matter is a little uneven. This is partly because the author tries to avoid becoming involved in discussing potential rather than realized commitment. The intriguing case of imaginal disk transdetermination in Drosophila is therefore dealt with somewhat superficially: although the author correctly emphasizes that
History of a contemporary revolution, part II Origins of Human Cancer: A Comprehensive Review edited by Joan Brugge, Tom Curran, Ed Harlow and Frank McCormick, Cold Spring Harbor Laboratory Press, 1991. $80.00 (xvi + 904 pages) ISBN 0 87969 404 1 The chapters of this book were contributed by speakers at the (second) 'Origins of Human Cancer' conference celebrating the Cold Spring Harbor (CSH) centennial in September 1990, although a handful of speakers at the meeting are not represented in the book. Three of the editors/organizers have a background in molecular biology of tumor viruses, yet the Origins no longer focuses so much on viral models of oncogenesis, but rather on issues where a common ground for epidemiology, basic research and clinical medicine has been reached. The chapters follow a minireview format with relatively few illustrations. The book is intended to provide easy reading, leaving many of the details and complexity of genes and' molecular interactions to its references.
322
AUGUST 1992
imaginal disk transdetermination cannot be explained simply as somatic mutation, he does not stress one very important aspect of the phenomenon, namely that it simultaneously involves an associated population of ceils within the disk. What is particularly good about the book, however, is that it catalogues and discusses a remarkable list of examples of trausdifferentiation, many of which have previously attracted little notice. For example, the production of lentoid and muscle tissue from pineal ceils was unknown to me, and probably to many others. Predictably, the great strength of the book lies in the review of crystallin synthesis and the control of the crystallin genes within lentoid and other cells, on which Professor Okada's laboratory has worked for some time. However, even in this intensively worked area, clear answers to the transdifferentiation enigma do not emerge. We learn, if we did not already know, that crystallin synthesis is not confined to lentoid or prelentoid tissue, and that many forms of crystallin closely resemble other cell proteins and are quite probably evolved from them [see the interesting review by Doolittle (1988) Nature (News and Views)
336, 18 on lens protein evolution]. So although cells that share a transdifferentiative relationship often have some active cell-specific genes in common, careful analysis of particular genetic programmes does not yield a plausible explanation for the phenomenon in question. I agree entirely with Tokindo Okada's conclusion that 'searching for master regulatory genes.., is essential in future transdifferentiation studies'. The myoD gene of muscle seems a possible candidate, but we will have to recognize many more before we have our fingers on the button that opens the black box of cell commitment. This readable and interesting book, which at £45 offers reasonable value, guides you and gives you some food for thought on the journey. However, it does not provide, nor pretend to provide, the understanding that, at least for this phenomenon, will be journey's end.
A meeting with the same title was held at CSH in 1976 and its proceedings were published in three volumes. However, Bob Weinberg declares in his introduction that 'a single report in Nature in March of 1976 changed it all'; the subsequent developments in molecular oncology have made it imperative to review the field 15 years on. The book begins logically with three overviews on oncogenes and suppressor genes, the genetics of human cancer and the challenges of the USA National Cancer Program. The introduction by Robert Weinberg is almost as enjoyable as his reputable talks at meetings. The two other chapters in thi s section also contain material that is repeated elsewhere in the book, a common problem in multi-author books entertaining so many related topics. The chapter on Progress and Challenges of the National Cancer Program seems to rush into treatments based on novel findings, at the expense of covering diagnostics, which has a more sound basis. It is also rare but eye-opening to see a sub-title on Cancer and Poverty in this chapter. The second section covers aspects of growth control in yeast, amphibian and insect cells. Sections 3 and 4 dwell on mutagenesis and carcinogenesis, as well as epidemiology and the genetics of
cancer predisposition. There is no separate chapter on tobacco, although the preface admits the magnitude of the problem; nicotine-derived nitrosamines are dealt with in later chapters. The molecular epidemiology of inherited susceptibility to breast carcinoma and the mutations of the adenomatous polyposis gene were not available at the time of the meeting and are therefore not included. A very important leap in molecular epidemiology I also missed in the book was the recent demonstration of how carcinogens leave their fingerprints in the gene encoding p53. One additional aspect, which is only mentioned in passing, is the role of endogenous mechanisms of carcinogenesis, especially 5-methylcytosine as an endogenous mutagen. Three sections on oncogenes and signal transduction are followed by sections on tumor-suppressor genes, hematopoiesis and leukemogenesis, selected organ-specific cancers, tumor development in transgenic mice and finally, a section on new approaches to therapy. The signal transduction dealt with here is from the pre-cyclin era, although cyclins appear in the chapter on the yeast cell cycle. A chapter on the immunotherapy of colon cancer seems a bit misplaced among the otherwise established topics. Similarly, chapters on
NORMAN MACLEAN School of Biological Sciences, Department of Biology, Biomedical Sciences Building, University of Southampton, Southampton, UK S09 3TU.
The commitment enigma Transdifferentiat~on: Flexibility in Cell Differentiation by T. S. Okada, Oxford University Press, 1991. £45100 (x + 238 pages) ISBN 0 19 854281 X A topic that has excited and perplexed biologists for more than a century is the confined but complex topic of transdifferentiation; that is, how cells change their state of differentiated commitment. Professor Okada's research group has worked in this area for many years. Although this compact, hardback monograph reviews numerous examples of this remarkable cellular phenomenon, the treatment of the subject matter is a little uneven. This is partly because the author tries to avoid becoming involved in discussing potential rather than realized commitment. The intriguing case of imaginal disk transdetermination in Drosophila is therefore dealt with somewhat superficially: although the author correctly emphasizes that
History of a contemporary revolution, part II Origins of Human Cancer: A Comprehensive Review edited by Joan Brugge, Tom Curran, Ed Harlow and Frank McCormick, Cold Spring Harbor Laboratory Press, 1991. $80.00 (xvi + 904 pages) ISBN 0 87969 404 1 The chapters of this book were contributed by speakers at the (second) 'Origins of Human Cancer' conference celebrating the Cold Spring Harbor (CSH) centennial in September 1990, although a handful of speakers at the meeting are not represented in the book. Three of the editors/organizers have a background in molecular biology of tumor viruses, yet the Origins no longer focuses so much on viral models of oncogenesis, but rather on issues where a common ground for epidemiology, basic research and clinical medicine has been reached. The chapters follow a minireview format with relatively few illustrations. The book is intended to provide easy reading, leaving many of the details and complexity of genes and' molecular interactions to its references.
322
AUGUST 1992
imaginal disk transdetermination cannot be explained simply as somatic mutation, he does not stress one very important aspect of the phenomenon, namely that it simultaneously involves an associated population of ceils within the disk. What is particularly good about the book, however, is that it catalogues and discusses a remarkable list of examples of trausdifferentiation, many of which have previously attracted little notice. For example, the production of lentoid and muscle tissue from pineal ceils was unknown to me, and probably to many others. Predictably, the great strength of the book lies in the review of crystallin synthesis and the control of the crystallin genes within lentoid and other cells, on which Professor Okada's laboratory has worked for some time. However, even in this intensively worked area, clear answers to the transdifferentiation enigma do not emerge. We learn, if we did not already know, that crystallin synthesis is not confined to lentoid or prelentoid tissue, and that many forms of crystallin closely resemble other cell proteins and are quite probably evolved from them [see the interesting review by Doolittle (1988) Nature (News and Views)
336, 18 on lens protein evolution]. So although cells that share a transdifferentiative relationship often have some active cell-specific genes in common, careful analysis of particular genetic programmes does not yield a plausible explanation for the phenomenon in question. I agree entirely with Tokindo Okada's conclusion that 'searching for master regulatory genes.., is essential in future transdifferentiation studies'. The myoD gene of muscle seems a possible candidate, but we will have to recognize many more before we have our fingers on the button that opens the black box of cell commitment. This readable and interesting book, which at £45 offers reasonable value, guides you and gives you some food for thought on the journey. However, it does not provide, nor pretend to provide, the understanding that, at least for this phenomenon, will be journey's end.
A meeting with the same title was held at CSH in 1976 and its proceedings were published in three volumes. However, Bob Weinberg declares in his introduction that 'a single report in Nature in March of 1976 changed it all'; the subsequent developments in molecular oncology have made it imperative to review the field 15 years on. The book begins logically with three overviews on oncogenes and suppressor genes, the genetics of human cancer and the challenges of the USA National Cancer Program. The introduction by Robert Weinberg is almost as enjoyable as his reputable talks at meetings. The two other chapters in thi s section also contain material that is repeated elsewhere in the book, a common problem in multi-author books entertaining so many related topics. The chapter on Progress and Challenges of the National Cancer Program seems to rush into treatments based on novel findings, at the expense of covering diagnostics, which has a more sound basis. It is also rare but eye-opening to see a sub-title on Cancer and Poverty in this chapter. The second section covers aspects of growth control in yeast, amphibian and insect cells. Sections 3 and 4 dwell on mutagenesis and carcinogenesis, as well as epidemiology and the genetics of
cancer predisposition. There is no separate chapter on tobacco, although the preface admits the magnitude of the problem; nicotine-derived nitrosamines are dealt with in later chapters. The molecular epidemiology of inherited susceptibility to breast carcinoma and the mutations of the adenomatous polyposis gene were not available at the time of the meeting and are therefore not included. A very important leap in molecular epidemiology I also missed in the book was the recent demonstration of how carcinogens leave their fingerprints in the gene encoding p53. One additional aspect, which is only mentioned in passing, is the role of endogenous mechanisms of carcinogenesis, especially 5-methylcytosine as an endogenous mutagen. Three sections on oncogenes and signal transduction are followed by sections on tumor-suppressor genes, hematopoiesis and leukemogenesis, selected organ-specific cancers, tumor development in transgenic mice and finally, a section on new approaches to therapy. The signal transduction dealt with here is from the pre-cyclin era, although cyclins appear in the chapter on the yeast cell cycle. A chapter on the immunotherapy of colon cancer seems a bit misplaced among the otherwise established topics. Similarly, chapters on
NORMAN MACLEAN School of Biological Sciences, Department of Biology, Biomedical Sciences Building, University of Southampton, Southampton, UK S09 3TU.