Polyploidization and Cancer

by Poon, Randy Y. C., Ph.D.

• ISBN13: 9781441961983
• ISBN10: 1441961984
• Edition: 1st
• Format: Hardcover
• Copyright: 2010-06-01
• Publisher: Landes Bioscience

Summary

Limiting genome replication to once per cell cycle is vital for maintaining genomestability. Although polyploidization is of physiologically importance for severalspecialized cell types, inappropriate polyploidization is believed to promote aneuploidyand transformation. A growing body of evidence indicates that the surveillancemechanisms that prevent polyploidization are frequently perturbed in cancers.Progress in the past several years has unraveled some of the underlying principlesthat maintain genome stability. This book brings together leaders of the field to overviewsubjects relating to polyploidization and cancer.

Table of Contents

Polyploidy, Aneuploidy and the Evolution of Cancer	p. 1
Abstract	p. 1
Introduction	p. 1
The Tetraploidy to Aneuploidy Progression in Carcinogenesis	p. 1
Tetraploidy and Aneuploidy in Barrett's Esophagus	p. 2
Not All Aneuploids Are Equal	p. 4
Why Do Cancer Cells Survive with Such Massive Alterations to Their Genome?	p. 5
Why Is Aneuploidy Common in Neoplastic Progression?	p. 7
DNA Damage Sensing by Linkage	p. 10
Ancient and Recent Cancer Genes	p. 10
Conclusion	p. 10
Molecular Mechanisms and Function of the Spindle Checkpoint, A Guardian of the Chromosome Stability	p. 15
Abstract	p. 15
Introduction	p. 15
Bipolar Attachment and Chromosome Congression	p. 16
Molecular Basis of the Spindle Checkpoint	p. 17
Activation of the Spindle Checkpoint Signaling	p. 19
Mad2 Template Model	p. 20
Phosphorylation and Spindle Checkpoint Function	p. 21
Silencing the Spindle Checkpoint	p. 22
Additional Surveillance System	p. 22
A Trigger of Tumorigenesis	p. 24
Conclusion	p. 24
Understanding Cytokinesis Failure	p. 27
Abstract	p. 27
Cytokinesis Occurs in Multiple Stages	p. 27
Positioning the Division Plane and Initiating Cytokinesis	p. 28
Ingression of the Cleavage Furrow	p. 30
Formation of the Midbody	p. 34
Abscission	p. 35
Regulation of Cytokinesis	p. 38
Coupling of Cytokinesis to Other Cellular Pathways	p. 42
Conclusion	p. 43
DNA Damage and Polyploidization	p. 57
Abstract	p. 57
Polyploidization and Cancer	p. 57
Mechanisms of Polyploidization	p. 58
The DNA Damage Checkpoints	p. 60
Polyploidization Induced by DNA Damage	p. 62
The Sensitivity of Polyploid Cells to DNA Damage	p. 64
Polyploidization and Cancer Therapies	p. 64
Conclusion	p. 65
Role of the p53 Family in Stabilizing the Genome and Preventing Polyploidization	p. 73
Abstract	p. 73
p53-Tumor Suppressor	p. 73
p53 and Genomic Stability	p. 74
Introduction to p73	p. 78
p73 Functions	p. 79
The Role of p73 in Genomic Stability	p. 80
Conclusion	p. 86
Centrosomes, Polyploidy and Cancer	p. 93
Abstract	p. 93
Introduction	p. 93
The Centrosome Duplication Cycle	p. 94
Aberrant Centrosome Numbers in Cancer Cells	p. 94
Multiple Pathways Can Lead to Aberrant Centrosome Numbers: Studies Using Human Papillomavirus (HPV) Oncoproteins	p. 95
Mechanisms of Centrosome Amplification in Tumor Cells	p. 96
Aberrant Centrosome Numbers as a Consequence of Polyploidy-Implications for Genomic Instability in Cancer	p. 99
Aberrant Centrosome Numbers as a Cause of Polyploidy	p. 100
Conclusion	p. 101
Polyploidy: Mechanisms and Cancer Promotion in Hematopoietic and Other Cells	p. 105
Abstract	p. 105
Overview: Characteristics of Polyploidy and Its Induction Under Different Conditions	p. 105
Prevalence of Polyploidy/Aneuploidy in Different Cancers	p. 107
Cancer Theories: Potential Involvement of Aneuploidy in Cancer Promotion	p. 108
Regulators of Mitosis and Mechanisms Leading to Aneuploidy	p. 109
Stem Cells and Cancer Development	p. 110
Chromosome Passenger Proteins and Their Role in Ploidy Promotion	p. 111
Chromosome Passenger Proteins and Cancer (Emphasis on the Role of Aurora-B)	p. 115
Conclusion	p. 116
Polyploidization of Liver cells	p. 123
Abstract	p. 123
Introduction	p. 123
Polyploidization During Normal (Developmental) Liver Growth	p. 124
Mechanism of Binucleation and Polyploidization	p. 126
Polyploidy in Regenerating Liver and During Pathological States	p. 130
Conclusion	p. 132
Analysis of Cellular DNA Content by Flow and Laser Scanning Cytometry	p. 137
Abstract	p. 137
Introduction	p. 137
Supravital Cell Staining	p. 140
DNA Staining after Disruption of Plasma Membrane	p. 141
DNA Staining in Fixed Cells	p. 142
Analysis of DNA in Paraffin-Embedded Samples	p. 143
Concurrent Analysis of Cell Surface Antigen and DNA Content	p. 143
Accuracy of DNA Content Measurement	p. 144
Accessibility of DNA in Chromatin to Fluorochromes	p. 144
Fluorochrome Binding to DNA-Mass Action Law	p. 145
Assessment of DNA Ploidy	p. 145
Conclusion	p. 146
Index	p. 149
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