Oncogenes by Geoffrey M. Cooper

Geoffrey M. Cooper
Release at: 1995
Pages: 774
Second Edition
File Size: 7 MB
File Type: pdf
Language: English

Content of Oncogenes by Geoffrey M. Cooper

Part I Introduction

The Cancer Cell

Biology of Human Cancers 3

Experimental Induction of Cancer in Animals 8

Growth of Cells in Culture 9

Growth Control and the Cell Cycle 12

Cell Transformation in Vitro 13

Biochemical Alterations in Transformed Cells 15

Summary 16

Part II Viral Oncogenes

Tumor Viruses

Hepatitis B Viruses

Simian Virus 40 and Polyomavirus






Summary 32

Retroviral Oncogenes

The src Gene of RSV 39

The RSV and ALV Genomes 42

Other Retroviral Oncogenes 44

Summary 47

The Origin of Retroviral Oncogenes

Isolation of Acutely Transforming Retroviruses 52

Normal Cell Homologs of Retroviral Oncogenes 53

Structure and Expression of Proto-oncogenes 56

Capture of Proto-oncogenes by Retroviruses 57

Viral Oncogenes are Altered Versions of Proto-


Summary 62

Part III Cellular Oncogenes and Tumor Suppressor Genes

Identification of Cellular Oncogenes by Gene Transfer

Transformation by Cellular DNA 69

Oncogenes of Human Tumors 72

Human Tumor Oncogenes and the ras Family 73

Mechanism of ras Oncogene Activation 75

Other Oncogenes Isolated by Gene Transfer 76

Summary 80

Cellular Oncogene Targets for Retroviral Integration

Tumor Induction by Retroviruses without Oncogenes 85

The Structure and Integration Sites of ALV Proviruses 87

in Lymphomas

Activation of c-myc in Bursal Lymphomas 89

Activation of Other Proto-oncogenes by Insertional


Identification of New Cellular Oncogenes as Targets for

Insertional Mutagenesis

Summary 94

Oncogenes and Chromosome Translocation

Chromosome Abnormalities in Neoplasms 99

Translocation of c-myc in Burkitt's Lymphomas and


The Philadelphia Translocation and abl 103

More TranslocationsMore Oncogenes 105

Summary 108

Amplification of Oncogenes in Tumors

Gene Amplification and Chromosome Abnormalities 113

Amplification of c-myc 114

New Members of the myc Gene Family 117

Amplification of erbB and erbB-2 118

Other Amplified Oncogenes 120

Summary 121

Retinoblastoma and the Discovery of Tumor Suppressor


Somatic Cell Hybridization 126

Inherited and Sporadic Retinoblastoma 128

Mapping the Retinoblastoma Gene 131

The Retinoblastoma Gene is Recessive at the Cellular


Molecular Cloning of the Rb Gene 137

Role of the Rb Gene in Other Neoplasms 139

Summary 141

Tumor Suppressor Genes in Human Neoplasms

The p53 Gene 145

Identification of Additional Tumor Suppressor Genes in

Colorectal Carcinomas

Tumor Suppressor Genes in Other Inherited Cancers 152

Candidates for Additional Tumor Suppressors 154

Summary 155

Role of Oncogenes and Tumor Suppressor Genes in the

Pathogenesis of Neoplasms

Biological Activities of Oncogenes in Vitro 163

Induction of Neoplasms by Oncogenes in Vivo 165

Oncogenes and Tumor Suppressor Genes in Tumors

Induced by Chemical Carcinogens

Oncogenes and Tumor Suppressor Genes in

Development of Human Neoplasms

Summary 177

Part IV Functions of Oncogenes and Tumor Suppressor Genes

Oncogenes and Growth Factors

Platelet-Derived Growth Factor and the sis Oncogene 183

A Family of Oncogenes Related to Fibroblast Growth Factors

The wnt Gene Family 188

Transforming Activity of Epidermal Growth Factor and TGF-

Hematopoietic Growth Factors as Oncogenes 189

Summary 191

Protein-Tyrosine Kinases and Growth Factor Receptors

Lessons from Src: Protein-Tyrosine Kinases 197

Growth Factor Receptors: Protein-Tyrosine Kinases and

Nonreceptor Protein-Tyrosine Kinases 206

Oncogenes Derived from Nontyrosine Kinase Receptors

Summary 214

Guanine Nucleotide Binding Proteins

G Proteins 222

Similarities between Ras and the G Proteins 227

Proteins that Regulate Ras 231

Targets of Ras 234

Summary 236

Protein-Serine/Threonine Kinases

The raf Oncogene Family 245

The Protein Kinase C Family 246

The mos Oncogene 249

Other Protein-Serine/Threonine Kinase Oncogenes 250

Summary 251

Transcription Factors

Oncogenes and Steroid Hormone Receptors 257

The Jun and Fos Families: Components of Transcription Factor AP-1

The Myc Family 264

Other Oncogene Transcription Factors 267

Tumor Suppressor Gene Products 270

Summary 272

Pathways of Mitogenic Signal Transduction

Receptor Tyrosine Kinases and Their Targets 280

Ras Activation 286

The Raf Protein-Serine/Threonine Kinase 288

The MAP Kinase Pathway 291

Transcription Factors and Alterations in Gene Expression

Summary 297

Regulation of the Cell Cycle

Cyclins and Cyclin-Dependent Kinases 307

Cyclin D: A Proto-oncogene Inducible by Growth


Cell Cycle Regulation of Rb 312

p53 and MTS1: Tumor Suppressors that Regulate Cdks 314

Role of p53 in Cell Cycle Arrest and Apoptosis Induced

by DNA Damage

Summary 317

Development, Differentiation, and Programmed Cell Death

Proto-oncogenes in Meiosis and Early Embryo


Role of the Ras/Raf Pathway in Development of Drosophila and C. elegans

Proto-oncogenes in Neuronal Differentiation 330

Developmental Roles of Other Proto-oncogenes 332

The bcl-2 Oncogene and Programmed Cell Death 336

Summary 338

Part V Clinical Applications

New Prospects for Cancer Prevention and Treatment 

Identification of Individuals with Inherited

Susceptibilities to Cancer

Role of Oncogenes in Cancer Diagnosis 349

Development of Drugs Targeted against Oncogenes 350

Summary 353

Glossary 357

Index 375

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