Breast Cancer in the Post-Genomic Era (eBook)

Preface 6
Contents 8
Contributors 10
1 The Genomic Basis of Breast Development and Differentiation 13
1. ARCHITECTURE OF THE HUMAN BREAST 13
2. CELL PROLIFERATION AND STEROID RECEPTOR CONTENT IN THE NORMAL BREAST 14
3. INFLUENCE OF AGE AND PARITY ON BREAST DEVELOPMENT AND CANCER SUSCEPTIBILITY 14
4. BREAST DEVELOPMENT AND THE PATHOGENESIS OF BREAST CANCER 15
5. GENOMIC APPROACH TO UNDERSTAND BREAST CANCER SUSCEPTIBILITY 17
6. CONCLUDING REMARKS 24
REFERENCES 25
2 Mammary Glands, Stem Cells, and Breast Cancer 31
1. BREAST DEVELOPMENTAL BIOLOGY AND TUMORIGENESIS 31
2. STEM CELL BIOLOGY IN THE MAMMARY GLAND 38
3. INFLUENCE OF THE MICROENVIRONMENT ON STEM CELL BIOLOGY AND CANCER 42
4. CLOSING REMARKS 46
REFERENCES 46
3 The Genetics of Breast Cancer: Application in Clinical Practice 51
Summary 51
1. INTRODUCTION 52
2. SPORADIC BREAST CANCER 52
3. HEREDITARY BREAST CANCER 56
REFERENCES 61
4 Alterations in Cell Cycle Regulatory Genes in Breast Cancer 67
1. CELL CYCLE: AN OVERVIEW 68
2. BREAST CANCER AND CELL CYCLE 79
REFERENCES 86
5 Neuregulins in the Nucleus 90
1. INTRODUCTION 90
2. OBSERVATIONS ON NRG IN THE NUCLEUS 91
3. NRG EXPERIMENTS 92
4. NRG FUNCTIONS IN THE NUCLEUS 93
REFERENCES 95
6 Role of the EGF-CFC Family in Mammary Gland Development and Neoplasia 98
1. EGF-CFC PROTEIN FAMILY: STRUCTURE AND POSTTRANSLATIONAL MODIFICATIONS 99
2. SIGNALING PATHWAYS ACTIVATED OR INHIBITED BY CRIPTO-1 101
3. NODAL/ALK4/ALK7/SMAD-2 SIGNALING PATHWAY 102
4. GLYPICAN-1/C-SRC/MAPK/AKT SIGNALING PATHWAY 103
5. CRIPTO-1 AND THE WNT SIGNALING PATHWAY 103
6. FUNCTION AND EXPRESSION OF EGF-CFC PROTEIN FAMILY DURING EMBRYONIC DEVELOPMENT 104
7. EGF-CFC PROTEINS IN MAMMARY GLAND DEVELOPMENT 104
8. CRIPTO-1 IN TRANSFORMATION AND TUMORIGENESIS OF MAMMARY EPITHELIUM 105
9. EXPRESSION OF CR-1 IN HUMAN BREAST CARCINOMAS 106
10. CONCLUSIONS 108
REFERENCES 108
7 Modeling Human Breast Cancer: The Use of Transgenic Mice 114
1. PROMOTERS 115
3. CONCLUSIONS 124
REFERENCES 125
8 Gene Expression Profiling in Breast Cancer: Clinical Applications 133
1. INTRODUCTION 133
2. MOLECULAR CLASSIFICATION 136
3. DIAGNOSIS AND PROGNOSIS 138
4. GENE EXPRESSION PROFILING FOR PREDICTION OF RESPONSE TO THERAPY 139
5. INTEGRATED DATA ANALYSIS OF MICROARRAY PLATFORMS 141
6. CONCLUSIONS 141
REFERENCES 143
9 TGF- b Signaling: A Novel Target for Treatment of Breast Cancer? 147
1. INTRODUCTION 147
2. THE TGF- ß SIGNALING PATHWAY 148
3. EFFECTS OF TGF- ß ON BREAST CANCER BIOLOGY 148
4. DICHOTOMY OF TGF- ß SIGNALING 153
5. TGF- ß AS A TARGET FOR BREAST CANCER THERAPY 154
REFERENCES 156
10 DNA Methylation in Breast Cancer 160
1. CHROMATIN, ITS MODIFICATIONS, AND CANCER 160
2. THE DNA METHYLATION PATTERN 162
3. MECHANISMS OF SILENCING OF GENE EXPRESSION BY DNA METHYLATION 163
4. DNA METHYLATION AND DEMETHYLATION ENZYMES 164
5. BILATERAL RELATIONSHIP BETWEEN CHROMATIN AND DNA METHYLATION 169
6. ABERRATIONS IN DNA METHYLATION IN BREAST CANCER 170
7. HYPERMETHYLATION OF GENES IN BREAST CANCER, ROLE IN SILENCING TUMOR SUPPRESSOR GENES 171
8. THERAPEUTIC IMPLICATION OF HYPERMETHYLATION OF GENES IN BREAST CANCER 172
9. HYPOMETHYLATION IN BREAST CANCER AND ITS THERAPEUTIC IMPLICATIONS 173
10. CONCLUSIONS AND PROSPECTIVE 176
REFERENCES 177
11 Signal Transduction Inhibitors in the Treatment of Breast Cancer 185
1. INTRODUCTION 186
2. MOLECULAR TARGETS IN BREAST CANCER 186
3. ANTI-EGFR DRUGS IN BREAST CANCER 189
4. VEGFR SIGNALLING INHIBITORS IN BREAST CANCER 193
5. INHIBITORS OF INTRACELLULAR SIGNAL TRANSDUCTION PATHWAYS 195
6. ENDOCRINE THERAPY IN COMBINATION WITH SIGNALLING INHIBITORS 198
7. CONCLUSIONS 201
REFERENCES 202
12 Integration of Target-Based Agents in Current Protocols of Breast Cancer Therapy 210
1. INTRODUCTION 211
2. TARGETING ERBB RECEPTORS 212
3. TARGETING ANGIOGENESIS 221
4. TARGETING MTOR 223
5. CONCLUSIONS 226
REFERENCES 226
Index 232