The biological function of clusterin (CLU, also known as ApoJ, SGP2, TRPM2, CLI) has been puzzling researchers since its discovery and characterization in the early 1980s. Approaches such as cloning, expression and functional characterization of the different protein products generated by the CLU gene have now produced a critical mass of information of tremendous biological importance that are teaching us an important lesson in molecular biology of gene expression regulation. This volume brings together the contributions of top researchers in the field, providing an overview and synthesis of the latest thought and findings relating to CLU.
1. I. Introduction 2. II. Briefly About Clinically Relevant Human PCa 3. III. CLU Signaling in Normal and Transformed Cell Lines 4. IV. CLU Expression in Human PCa 5. V. Castration Resistant and Metastatic PCa: The Challenge of CLU Antisense Therapy 6. VI. Chemoprevention of PCa: A Role for CLU in the Mechanism of Action of GTCs 7. VII. CLU as Tumor Modulator: Is CLU a Novel Tumor Suppressor Gene? 8. VIII. Conclusions 9. Acknowledgments 10. The Role of Clusterin (CLU) in Malignant Transformation and Drug Resistance in Breast Carcinomas 11. Abbreviations 12. I. Introduction 13. II. Localization of CLU in Breast Carcinomas 14. III. Relationship Between Cytoplasmic CLU and Apoptosis in Breast Carcinomas 15. IV. Role of CLU in Tumorigenesis and Progression of Breast Carcinomas 16. V. Prognostic Significance of CLU Expression in Breast Carcinomas 17. VI. CLU and Resistance to Treatment in Breast Carcinomas 18. VII. Conclusions 19. Acknowledgments 20. CLU and Colon Cancer. The Dual Face of CLU 21. I. Introduction: Genes and Proteins in Colorectal Cancer 22. II. Genetic Instability and Control of DNA Damage: DNA Double-Strand Breaks Repair 23. III. Clonal Expansion: Apoptosis Inhibition 24. IV. CLU in Colorectal Cancer Progression: sCLU and Apoptosis Escape 25. V. CLU as a New Biomarker for Colon Cancer Screening 26. VI. Conclusions and Future Perspectives 27. Clusterin (CLU) and Lung Cancer 28. I. Introduction 29. II. Carcinogenesis 30. III. Progression/Metastasis 31. IV. Treatment 32. V. CLU Expression and Prognosis in Patients with Lung Cancer 33. VI. Conclusions 34. Acknowledgments 35. Clusterin and Chemoresistance 36. I. Introduction 37. II. Association of sCLU with Chemoresistance 38. III. Association of sCLU with Multidrug Resistance 39. IV. Association of sCLU with Resistance to Irradiation and Oxidative Stress 40. V. Association of sCLU with Progressive Tumors 41. VI. Association of sCLU with Resistance to Targeted Therapy (TNF, FAS, TRAIL, HDAC Inhibitors, Herceptin) 42. VII. Induction by Genotoxic and Oxidative Stresses 43. VIII. Mechanism of Induction of and Cytoprotection by CLU 44. IX. Strategies to Blockade CLU for Chemosensitization in Cancer Cells 45. CLU “In and Out” 46. I. Introduction 47. II. Normal and Cancer Microecosystem 48. III. Microenvironment Effects on CLU Expression (the “IN” Effect) 49. IV. sCLU Effects on Microenvironment (the “OUT” Effect): Up- and Downstream Signals 50. V. Conclusions and Future Perspectives 51. Regulation of CLU Gene Expression by Oncogenes and Epigenetic Factors 52. I. Introduction 53. II. Regulation of CLU Expression by Transforming Oncogenes: Early Evidence 54. III. Regulation of CLU Expression by Protooncogenic Transcription Factors 55. IV. Oncogenic Signaling and Epigenetic Regulation of CLU Expression 56. V. Concluding Remarks 57. Acknowledgments 58. Conclusions and Perspectives 59. I. Introduction 60. II. Take Home Messages from Chapters of Vols. 104 and 105 61. III. General Consensus 62. IV. Open Issues 63. V. Possible Clinical Implementations 64. VI. Future Research 65. Acknowledgments
The biological function of clusterin (CLU, also known as ApoJ, SGP2, TRPM2, CLI) has been puzzling researchers since its discovery and characterization in the early 1980s. Approaches such as cloning, expression and functional characterization of the different protein products generated by the CLU gene have now produced a critical mass of information of tremendous biological importance that are teaching us an important lesson in molecular biology of gene expression regulation. This volume brings together the contributions of top researchers in the field, providing an overview and synthesis of the latest thought and findings relating to CLU.
1. I. Introduction 2. II. Briefly About Clinically Relevant Human PCa 3. III. CLU Signaling in Normal and Transformed Cell Lines 4. IV. CLU Expression in Human PCa 5. V. Castration Resistant and Metastatic PCa: The Challenge of CLU Antisense Therapy 6. VI. Chemoprevention of PCa: A Role for CLU in the Mechanism of Action of GTCs 7. VII. CLU as Tumor Modulator: Is CLU a Novel Tumor Suppressor Gene? 8. VIII. Conclusions 9. Acknowledgments 10. The Role of Clusterin (CLU) in Malignant Transformation and Drug Resistance in Breast Carcinomas 11. Abbreviations 12. I. Introduction 13. II. Localization of CLU in Breast Carcinomas 14. III. Relationship Between Cytoplasmic CLU and Apoptosis in Breast Carcinomas 15. IV. Role of CLU in Tumorigenesis and Progression of Breast Carcinomas 16. V. Prognostic Significance of CLU Expression in Breast Carcinomas 17. VI. CLU and Resistance to Treatment in Breast Carcinomas 18. VII. Conclusions 19. Acknowledgments 20. CLU and Colon Cancer. The Dual Face of CLU 21. I. Introduction: Genes and Proteins in Colorectal Cancer 22. II. Genetic Instability and Control of DNA Damage: DNA Double-Strand Breaks Repair 23. III. Clonal Expansion: Apoptosis Inhibition 24. IV. CLU in Colorectal Cancer Progression: sCLU and Apoptosis Escape 25. V. CLU as a New Biomarker for Colon Cancer Screening 26. VI. Conclusions and Future Perspectives 27. Clusterin (CLU) and Lung Cancer 28. I. Introduction 29. II. Carcinogenesis 30. III. Progression/Metastasis 31. IV. Treatment 32. V. CLU Expression and Prognosis in Patients with Lung Cancer 33. VI. Conclusions 34. Acknowledgments 35. Clusterin and Chemoresistance 36. I. Introduction 37. II. Association of sCLU with Chemoresistance 38. III. Association of sCLU with Multidrug Resistance 39. IV. Association of sCLU with Resistance to Irradiation and Oxidative Stress 40. V. Association of sCLU with Progressive Tumors 41. VI. Association of sCLU with Resistance to Targeted Therapy (TNF, FAS, TRAIL, HDAC Inhibitors, Herceptin) 42. VII. Induction by Genotoxic and Oxidative Stresses 43. VIII. Mechanism of Induction of and Cytoprotection by CLU 44. IX. Strategies to Blockade CLU for Chemosensitization in Cancer Cells 45. CLU “In and Out” 46. I. Introduction 47. II. Normal and Cancer Microecosystem 48. III. Microenvironment Effects on CLU Expression (the “IN” Effect) 49. IV. sCLU Effects on Microenvironment (the “OUT” Effect): Up- and Downstream Signals 50. V. Conclusions and Future Perspectives 51. Regulation of CLU Gene Expression by Oncogenes and Epigenetic Factors 52. I. Introduction 53. II. Regulation of CLU Expression by Transforming Oncogenes: Early Evidence 54. III. Regulation of CLU Expression by Protooncogenic Transcription Factors 55. IV. Oncogenic Signaling and Epigenetic Regulation of CLU Expression 56. V. Concluding Remarks 57. Acknowledgments 58. Conclusions and Perspectives 59. I. Introduction 60. II. Take Home Messages from Chapters of Vols. 104 and 105 61. III. General Consensus 62. IV. Open Issues 63. V. Possible Clinical Implementations 64. VI. Future Research 65. Acknowledgments
