Genetics of Cancer (eBook)

Front Cover 1
The Genetics of Cancer 4
Copyright Page 5
Contents 6
Preface 12
Abbreviations 16
Chapter 1. Introduction 20
Chapter 2. Clonal evolution of the metastatic phenotype 23
Manifestation of genetic instability 24
Chromosomal abnormalities in cancer 25
Clonal expansion of tumour cell subpopulations 27
Genetic instability and the generation of metastatic variants 28
DNA repair and repair fidelity in metastatic variants 30
Genetic recombination in the generation metastatic variants 32
Microsatellite instability in cancer progression 34
Telomerase function, genetic instability, cell proliferation and cancer metastasis 39
Chapter 3. Inefficiency of the metastatic process 42
Chapter 4 Tumour growth and metastatic potential 44
Chapter 5. Cell cycle regulation and pathogenesis of cancer 46
The regulatory role of p53 in G1-S and G2-M transition in cell cycle progression 47
Genomic organisation of the p53 gene 48
p53 abnormalities and dysfunction 49
Regulation of p53 function 50
p53, cancer progression and prognosis 52
Subcellular localisation of p53 protein 58
p53 protein as a transcription factor 60
Alternative splicing of the p53 gene transcript 61
Regulation of mdm2 by p53 62
mdm2 abnormalities in cancer 62
mdm2 and tumour progression 64
Transactivation of growth factor receptor genes by p53 65
GADD genes and their regulation by p53 65
Metastasis-associated 18A2/mtsl gene in cell cycle progression 67
Retinoblastoma susceptibility gene (rb) abnormalities in cancer 69
Cyclins, cell cycle progression and cyclins as proto-oncogenes 75
Cyclin-dependent kinase (cdk) inhibitors as tumour suppressors 78
Structural and functional features of group 1 cdk inhibitors 79
Regulation of waf1/cip1 gene expression by p53 79
Is the waf1/cip1 gene altered in cancer? 82
Response of kip1/kip2 genes to antiproliferative signals 83
kip1 gene expression in neoplasia 84
p16/ink4 putative multiple tumour suppressor gene in tumour development and progression 85
Heat shock proteins (HSPs) in development, differentiation and tumorigenesis 87
Chapter 6. Apoptosis in tumour growth and metastasis 95
The nature of apoptotic changes 96
Genetic regulation of apoptosis 96
Chapter 7. Angiogenesis in cancer 105
Induction of neovascularisation by tumours 105
Inhibitors of neovascularisation 113
Angiogenesis as a predictor of prognosis of cancer 115
Chapter 8. Cell surface glycoproteins and their receptors 119
Integrin receptors and their function 119
Vitronectin receptors 120
Laminin receptors 121
Cadherins 122
Tenascin 126
CD44 and its isoforms 126
Cell adhesion molecules (CAMs) in cancer invasion 132
Chapter 9. Proteinases and their inhibitors in cancer invasion 142
Urokinase in cancer invasion and metastasis 144
Cathepsins in cancer invasion and progression 147
Matrix metalloproteinases (MMPs) in cancer 154
Chapter 10. Oncogenes and cancer metastasis 163
The ras oncogene in tumorigenesis 165
Erb genes as predictors of cancer progression and prognosis 166
Epidermal growth factor receptors in cancer 172
Chapter 11. Developmental genes and their putative suppressor function 174
wnt genes in cell differentiation and neoplasia 175
Wilms' tumour gene wt1 in embryonic development and neoplasia 182
Chapter 12. Tumour suppressor genes 190
Progression of colorectal neoplasia 191
BRCA1 tumour suppressor (breast and ovarian carcinoma susceptibility) gene 196
DPC/BRCA2 tumour suppressor genes 200
Chapter 13. Metastasis suppressor genes 202
The putative metastasis suppressor function of the nm23 gene 203
Chapter 14. Dominant metastasis-associated genes 209
mta1 gene expression in mammary carcinoma and adenocarcinoma cell lines 209
The role of murine 18A2/mts1 homologues and other S-100 proteins in cancer progression 210
Cell differentiation and 18A2/mts1 gene expression 217
Are 18A2/mts1 and nm23 genes functionally related? 219
18A2/mts1 and nm23 genes and cytoskeletal integrity 219
The role of cytoskeletal elements in cancer invasion 221
Growth factor receptors are associated with cytoskeletal elements 222
The p21 ras protein and the transduction of 18A2-mts1/b-mts1 proliferative signals 223
Molecular mechanisms of regulation of metastasis by 18A2/mts1 gene and its homologues 224
Epilogue 230
References 234
Index 346