Advances in Cancer Research (eBook)

Cover 1
Contents 6
Contributors to Volume 66 11
Chapter 1. Foundations in Cancer Research: The Adventures of a Biologist: Prenatal Diagnosis, Hematopoiesis,Leukemia, Carcinogenesis, and Tumor Suppression 14
I. Studies in England and Move to Israel: Amniocentesis and Prenatal Diagnosis on Amniotic Fluid Cells 14
II. Hematopoiesis and Lcukemia 16
III. Carcinogenesis: Tumor Viruses, Chemical Carcinogens, and Irradiation 34
IV. Chromosome Changes and Tumor suppression 37
V. Concluding Remarks 41
VI. Short Curriculum Vitae 43
References 44
Chapter 2. Foundations in Cancer Research: From Aristotle, through Spemann, to Tumor Immunology: A Personal Experience 54
I. Dreams 55
II. Initial Experiments: Tumor Allografts 57
III. Initial Realities: Tumor-Specific Transplantation Antigen 59
IV. Actual Realities: T Cell Recognition of cell Surface Epitopes 60
V. MHC Class I Genes Control the metastatic Phenotype of Tumor Cells 62
VI. Upregulating the Expression of Endogenous H-2K Genes 66
VII. The Tumor-Specific Immunogenic Epitope of a Murine Lung Carcinoma Is an Octapeptide Mutein of Connexin 37 68
VIII. The New Era of Molecularly Characterized Tumor- Associated Antigens 69
IX. Tumor Cells Transduced by Cytokine Genes 72
X. Target Organ Specificity of Metastasis 76
XI. Conclusion 77
References 79
Chapter 3. Tumor Suppressor p53 Mutations and Breast Cancer: A Critical Analysis 84
I. Introduction 85
II. Somatic Changes in Human Breast Cancer 85
III. History of p53 86
IV. The p53 Gene 88
V. The p53 Protein 90
VI. Quaternary Structure of the p53 Protein 95
VII. Functional Properties of WT p53 98
VIII. Properties and Phenotypes of p53 Mutants 111
IX. p53 Mutations and Breast Cancer 121
X. Systems for Studying Genetic Changes Involved in Breast Cancer 133
XI. Summary 139
References 139
Chapter 4. p53: A Cell Cycle Regulator Activated by DNA Damage 156
I. Introduction 156
II. Biological Activiteis of p53 157
III. Biochemical Functions of p53 162
IV. Interactions with Viral and Cellular Proteins 174
V. Regulation of p53 Function 179
References 186
Chapter 5. Cyclins and Cyclin-Dependent Kinases: Theme and Variations 194
I. Introduction 194
II. Checkpoints and the Cell Cycle 195
III. Cyclins 196
IV. Cyclins Are Regulated by Proteolysis 196
V. How CDKs Are Activated by Binding Cyclins 200
VI. Modulation of the Cyclic–CDK Complexes: Phosphorylation and Inhibitor Proteins 201
VII. START 205
VIII. Fission Yeast START 207
IX. Mammalian START 209
X. D-Type Cyclins as Regulators of Rb 210
XI. D-Type Cyclins are Involved in Differentiation 211
XII. The G1 to S Cyclins 212
XIII. S-Phase Cyclins 214
XIV. Mitotic Cyclins 216
XV. Nonmitotic Cell Cyclins 218
XVI. With Apologies to Elgar 219
References 219
Chapter 6. Molecular Genetics of 11q23 Chromosome Translocations 226
I. Introduction 226
II. Cytogenetics of 11q23 Abnormalities 227
III. Clinical Considerations 229
IV. Cloning the Breakpoint Cluster Region 230
V. ALL-1: The Human Homologue of Drosophila trithorax 236
VI. Fusion of ALL-1 to Partner Genes 239
VII. Models for ALL-1 Leukemogenicity 244
VIII. Conclusions 245
References 246
Chapter 7. Role of Scatter Factor and the c-met Protooncogene in the Pathogenesis of AIDS-Associated Kaposi’s Sarcoma 250
I. Introduction 250
II. Epidemiology of AIDS-Associated Kaposi’s Sarcoma 251
III. Agents Implicated in the Etiology of Kaposi,s Sarcoma 252
IV. The Kaposi’s Sarcoma Phenotype 253
V. Endothelial Cells Undergo Phenotypic Conversion to Kaposi’s Sarcoma-like Tumor Cells When Exposed to HIV-Infected T Lymphocyte-Conditioned Media 255
VI. Scatter Factor and the c-met Receptor: A Paracrine and Autocrine Growth Signaling System 262
VII. Proposed Role for Scatter Factor and c-met in Kaposi's Sarcoma Carcinogenesis 263
VIII. Conclusions and Summary 266
References 267
Chapter 8. REL/NF-kB/1kB Story 272
I. Introduction 272
II. .B-Binding Factors 274
III. I.B Family of Proteins 283
IV. Regulation of Rel/NF-.B Activity 290
V. Rel/NF-.B Regulation of'the Target Gene Transcription 297
VI. Drosophila System: Dorsal, Dif, and Cactus 299
VII. Concluding Remarks 302
References 302
Chapter 9. Radiation Leukemia Virus-Induced Leukemogenesis: A Paradigm of Preleukemia and Its Control by Preventive Therapy 310
I. Introduction 310
II. Tumorigenesis Induced by Chronic Retroviruses 311
III. Radiation Leukemia Virus (RadLV)-Induced Leukemogenesis 312
IV. Mechanism of Transformation by RadLV 314
V. RadLV-Induced Preleukemic (PL) Cells 316
VI. PL Cell Cultures 318
VII. Clonal Nature of PL Cells 319
VIII. IL-4 Dependency of PL Cells 319
IX. Active Intervention in RadLV Leukemogenesis 322
X. Conclusion 325
References 326
Chapter 10. The Insertion of Foreign DNA into Mammalian Genomes and Its Consequences: A Concept in Oncogenesis 330
I. Scope of Review 330
II. The Adenovirus System as a Model 333
III. On the Mechanism of Integrative Recombination 343
IV. De novo DNA Methylation of Integrated Foreign DNA 348
V. Alterations in Patterns of Cellular DNA Methylation and Gene Expression as Consequences of Foreign DNA Insertions into Mammalian Genomes? 355
VI. Uptake of Foreign DNA through the Gastrointestinal Tract 357
VII. A Concept for Oncogenesis„Implications for Gene Therapy and Research on Transgenic Organisms 358
References 360
Index 364