Clusterin, Part B (eBook)

Front Cover 1
Advances in Cancer Research 4
Copyright 5
Contents 6
Contributors 10
Chapter 1: Clusterin (CLU) and Prostate Cancer 12
I. Introduction 12
II. Briefly About Clinically Relevant Human PCa 13
III. CLU Signaling in Normal and Transformed Cell Lines 15
IV. CLU Expression in Human PCa 16
V. Castration Resistant and Metastatic PCa: The Challenge of CLU Antisense Therapy 18
VI. Chemoprevention of PCa: A Role for CLU in the Mechanism of Action of GTCs 20
VII. CLU as Tumor Modulator: Is CLU a Novel Tumor Suppressor Gene? 22
VIII. Conclusions 23
Acknowledgments 26
References 26
Chapter 2: The Role of Clusterin (CLU) in Malignant Transformation and Drug Resistance in Breast Carcinomas 32
I. Introduction 33
II. Localization of CLU in Breast Carcinomas 34
III. Relationship Between Cytoplasmic CLU and Apoptosis in Breast Carcinomas 35
IV. Role of CLU in Tumorigenesis and Progression of Breast Carcinomas 36
V. Prognostic Significance of CLU Expression in Breast Carcinomas 41
VI. CLU and Resistance to Treatment in Breast Carcinomas 42
VII. Conclusions 47
Acknowledgments 48
References 48
Chapter 3: CLU and Colon Cancer. The Dual Face of CLU: From Normal to Malignant Phenotype 56
I. Introduction: Genes and Proteins in Colorectal Cancer 57
II. Genetic Instability and Control of DNA Damage: DNA Double-Strand Breaks Repair 58
III. Clonal Expansion: Apoptosis Inhibition 60
IV. CLU in Colorectal Cancer Progression: sCLU and Apoptosis Escape 61
V. CLU as a New Biomarker for Colon Cancer Screening 67
VI. Conclusions and Future Perspectives 69
References 71
Chapter 4: Clusterin (CLU) and Lung Cancer 74
I. Introduction 75
II. Carcinogenesis 76
III. Progression/Metastasis 78
IV. Treatment 79
V. CLU Expression and Prognosis in Patients with Lung Cancer 82
VI. Conclusions 83
Acknowledgments 85
References 85
Chapter 5: Clusterin and Chemoresistance 88
I. Introduction 89
II. Association of sCLU with Chemoresistance 89
III. Association of sCLU with Multidrug Resistance 92
IV. Association of sCLU with Resistance to Irradiation and Oxidative Stress 93
V. Association of sCLU with Progressive Tumors 94
VI. Association of sCLU with Resistance to Targeted Therapy (TNF, FAS, TRAIL, HDAC Inhibitors, Herceptin) 95
VII. Induction by Genotoxic and Oxidative Stresses 96
VIII. Mechanism of Induction of and Cytoprotection by CLU 97
IX. Strategies to Blockade CLU for Chemosensitization in Cancer Cells 99
References 100
Chapter 6: CLU "In and Out": Lookingfor a Link 104
I. Introduction 105
II. Normal and Cancer Microecosystem 107
III. Microenvironment Effects on CLU Expression (the "IN" Effect) 109
IV. sCLU Effects on Microenvironment (the "OUT" Effect): Up- and Downstream Signals 119
V. Conclusions and Future Perspectives 122
References 122
Chapter 7: Regulation of CLU Gene Expression by Oncogenes and Epigenetic Factors: Implications for Tumorigenesis 126
I. Introduction 127
II. Regulation of CLU Expression by Transforming Oncogenes: Early Evidence 130
III. Regulation of CLU Expression by Protooncogenic Transcription Factors 132
IV. Oncogenic Signaling and Epigenetic Regulation of CLU Expression 136
V. Concluding Remarks 137
Acknowledgments 138
References 138
Chapter 8: Conclusions and Perspectives 144
I. Introduction 144
II. Take Home Messages from Chapters of Vols. 104 and 105 145
III. General Consensus 153
IV. Open Issues 155
V. Possible Clinical Implementations 156
VI. Future Research 159
Acknowledgments 160
References 160
Index 162
Color Plate 166