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Medicine - Oncology & Hematology | Molecular Basis of Breast Cancer - Prevention and Treatment

Molecular Basis of Breast Cancer

Prevention and Treatment

Russo, Jose, Russo, Irma H.

Softcover reprint of the original 1st ed. 2004, XIV, 448 p.

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  • Up-to-date information on the molecular basis of breast cancer
  • Extremely helpful both for clinicians treating patients and for researchers looking for new venues of development
book, whose goal is to comprehensively review in ten During the past 30 years we have witnessed the emer­ chapters the fundamental knowledge on breast can­ gence of new disciplines whose contribution to the understanding of the biology of breast cancer have cer. The opening chapter links epidemiology, influ­ been enormous. Advances in the field of steroid hor­ ence of geographic and environmental exposures on mone nuclear receptors, which control the expression cancer incidence to the development of the organ and of genetic programs involved in cellular processes its role in cancer initiation. Central to this approach that are essential for normal and aberrant cell is the endocrine control of breast development, the growth, have been major contributors to the therapy relationship of cell proliferation with the presence of and prevention of hormone-dependent cancers. The steroid hormone receptors in the breast epithelium, and finally the importance of full differentiation as a discoveries of the association of hereditary breast cancers with mutations in the BRCAl and BRCA2 tool for protecting the breast from developing cancer. genes, and the concept that they essentially represent Reported are studies of the pathogenesis of breast a continuum of mutations with different degrees of cancer that have elucidated the site of origin of breast penetrance within given families, have added consid­ cancer and have been validated by in vitro experi­ erable understanding to the molecular basis of breast mentation.

Content Level » Research

Keywords » Breast - Differentiation - Treatment - cancer - pathogenesis - prevention

Related subjects » Cancer Research - Gynecology - Oncology & Hematology

Table of contents 

1 Epidemiological Considerations in Breast Cancer.- 1.1 Introduction.- 1.2 Geographical Influences.- 1.3 Radiation as an Etiologic Agent.- 1.4 Electromagnetic Fields.- 1.5 Environmental Pollutants.- 1.6 Reproductive Factors.- 1.7 Environmental Exposures at a Young Age that Increase the Risk of Breast Cancer.- 1.7.1 Endocrinological Milieu.- 1.7.2 Smoking.- 1.7.3 Alcohol as a Neuroendocrine Disruptor.- 1.7.4 Effect of Light on Puberty and Breast Cancer Risk.- 1.8 Conclusions.- References.- 2 The Breast as a Developing Organ.- 2.1 Introduction.- 2.2 Prenatal and Perinatal Development.- 2.3 Postnatal Development.- 2.4 Pregnancy.- 2.5 Postlactational Changes.- 2.6 The Menopausal Breast.- 2.7 Parenchyma-Stroma Relationship.- 2.8 Genetic Influences in Breast Development.- 2.9 Cell Proliferation and Hormone Receptors in Relation to Breast Structure.- 2.10 Extracellular Matrix Protein Expression in the Normal Breast.- 2.10.1 Angiogenic Index in the Lobular Structures.- 2.10.2 Elastininthe Lobular Structures.- 2.10.3 Tenascin in the Lobular Structures.- 2.11 Genomic Profile of Lobular Structures in Nulliparous and Parous Women’s Breasts.- 2.12 Novel Differentiation-Associated Serpin is Upregulated During Lobular Development.- 2.13 Mammary-Derived Growth Inhibitor.- 2.14 Conclusions.- References.- 3 Endocrine Control of Breast Development.- 3.1 Introduction.- 3.2 Steroid Receptors, Cell Proliferation, and Breast Differentiation.- 3.2.1 Relationship of Proliferating and ERa-Positive Cells in the Human Breast.- 3.2.2 Cell Proliferation, ERct, and PgR Content in the Rat Mammary Gland.- 3.2.3 Biological Significance.- 3.3 Human Chorionic Gonadotropin as a Differentiating Agent in the Human Breast and in the Rodent Mammary Gland.- 3.3.1 Evidence for a Receptor for Human Chorionic Gonadotropin in Human Breast Epithelial Cells.- 3.3.2 Human Chorionic Gonadotropin Receptor in the Rat Mammary Gland.- 3.3.3 Biological Significance of the LH/hCG Receptor.- 3.4 Effect of Human Chorionic Gonadotropin on Human Breast Epithelial Cells.- 3.4.1 Effect on Protein Synthesis and In Vitro Translational Products of mRNA.- 3.4.2 Effect of Human Chorionic Gonadotropin Treatment on Inhibin Synthesis.- 3.4.3 Effect of Hormones on the Proliferative Activity of Cultured Normal and Neoplastic Human Breast Epithelial Cells.- 3.4.4 Biological Significance of the hCG-Inhibin Pathway.- 3.5 Homeobox Genes’ Expression and Their Modulation by Human Chorionic Gonadotropin in Human Breast Epithelial Cells.- 3.5.1 Class I Homeobox Gene Expression in Human Breast Epithelial Cell Lines.- 3.5.2 Human Chorionic Gonadotropin Modulates Expression of Homeobox Genes.- 3.5.3 Human Chorionic Gonadotropin and HOXA2 Inhibit AP-1.- 3.6 Human Chorionic Gonadotropin and Histone Acetylation.- 3.7 Conclusions.- References.- 4 The Role of Estrogen in Breast Cancer.- 4.1 Introduction.- 4.2 Sources of Estrogens in Human Breast Tissue.- 4.3 Role of Estrogens in Human Breast Proliferation.- 4.4 Estrogens in Human Breast Carcinogenesis.- 4.4.1 Receptor-Mediated Pathway.- 4.4.2 Oxidative Metabolism of Estrogen.- 4.4.2.1 Estrogen as Mutagenic Agents.- 4.4.2.2 The Mechanism by Which Estrogens Induce Mutations.- 4.4.2.3 Additional Factors Contributing to the Carcinogenic Effect of Estrogen.- 4.4.3 Estrogens as Inducers of Aneuploidy.- 4.5 Biological Demonstration That Estrogens Are Carcinogenic in the Human Breast.- 4.5.1 The Proof of Principle.- 4.5.2 The In Vitro Model of Cell Transformation.- 4.5.2.1 Transformation Effect of Estrogen in MCF-10F Cells.- 4.5.2.2 Transformation Effect of the Estrogen Metabolites.- 4.5.2.3 Role of Antiestrogens in the Expression of the Transformation Phenotype.- 4.5.2.4 Detection of Estrogen Receptors in MCF 10F-Cells.- 4.5.2.5 Evidence for a Role of ER? and Metabolic Activation of Estrogen in the Transformation of Human Breast Epithelial Cells.- 4.5.3 Genomic Changes Induced by Estrogen and Its Metabolites in Human Breast Epithelial Cells.- 4.5.4 Other Genomic Changes Induced by Estrogen and Its Metabolites in the Transformation of Human Breast Epithelial Cells.- 4.5.5 Chromosomal Alterations Induced by Estrogen and Its Metabolites.- 4.6 A Unified Concept in the Role of Estrogen in Breast Cancer.- References.- 5 Pathogenesis of Breast Cancer.- 5.1 Introduction.- 5.2 The Site of Origin of Breast Cancer.- 5.3 Supporting Evidence for the Site of Origin of Breast Cancer.- 5.3.1 In Vitro Studies.- 5.3.2 Breast Architecture as a Determining Factor in the Susceptibility of the Human Breast to Cancer.- 5.3.3 Specific Considerations on the Relation Between Lobular Development and Familial Breast Cancer-Related Genes.- 5.3.4 Unifying Concepts.- 5.4 Molecular Changes in the Initiation and Progression of Breast Cancer.- 5.4.1 Differential Expression of Human Ferritin H Chain Gene and Breast Cancer.- 5.4.2 S100P Calcium-Binding Protein as a Marker of Cancer Initiation.- 5.4.3 Role of Intracellular Ca2+ During Cell Immortalization and Cell Transformation.- 5.4.4 The Role of Ca Intracellular and S100 Protein Expression in the Formation of Microcal-cifications in Preneoplastic and Neoplastic Lesions of the Breast.- 5.5 Genetic Changes Associated with Initiation and Progression of Breast Cancer.- 5.5.1 Laser Capture Microdissection.- 5.5.2 Microsatellite Instability and Loss of Heterozygosity in Microdissected Lesions of the Breast.- 5.5.3 Example of Breast Cancer Genetic Heterogeneity Revealed by Laser Capture Microdissection Technique.- 5.6 Summary and Conclusions.- References.- 6 Animal Models for Human Breast Cancer.- 6.1 Introduction.- 6.2 General Concepts.- 6.3 Chemically-Induced Mammary Tumorigenesis.- 6.4 Radiation-Induced Mammary Tumorigenesis.- 6.5 Genetic Background and Mammary Carcinogenesis.- 6.6 Pathogenesis of Rat Mammary Tumors.- 6.7 Mammary Gland Differentiation as a Modulator of Carcinogenic Response.- 6.7.1 Cell of Origin of Rat Mammary Carcinomas.- 6.7.2 Cell Kinetics and Mammary Carcinogenesis.- 6.7.3 Role of the Stroma in the Pathogenesis of Mammary Cancer.- 6.8 Pathological Classification of Rat Mammary Tumors.- 6.8.1 Epithelial Neoplasms.- 6.8.1.1 Intraductal Papilloma.- 6.8.1.2 Papillary Cystadenoma.- 6.8.1.3 Adenoma.- 6.8.1.4 Precancerous Lesions: Intraductal Proliferation.- 6.8.1.5 Carcinoma In Situ.- 6.8.1.6 Invasive Ductal Carcinomas.- 6.8.2 Stromal Neoplasms.- 6.8.2.1 Fibroma.- 6.8.2.2 Fibrosarcoma.- 6.8.3 Epithelial-Stromal Neoplasms.- 6.8.3.1 Fibroadenoma.- 6.8.3.2 Carcinosarcoma.- 6.8.4 Nonneoplastic Lesions.- 6.9 Differential Diagnosis of Mammary Tumors.- 6.9.1 Macroscopic Criteria.- 6.9.2 Histopathological Criteria.- 6.9.3 Biological Criteria.- 6.10 Biological Importance of the Chemical Carcinogen-Induced Rat Mammary Tumor Model.- 6.11 Genetically Engineered Mice Model.- 6.11.1 Anatomy of the Mouse Mammary Gland.- 6.11.2 Classification of Genetically Engineered Mouse Mammary Lesions.- 6.11.2 Comparative Pathology of the Model Systems.- References.- 7 In Vitro Models for Human Breast Cancer.- 7.1 Introduction.- 7.2 Growth Properties of Normal Human Breast Epithelial Cells In Vitro.- 7.3 The MCF-7 Cell as a Model of Human Breast Cancer In Vitro.- 7.3.1 Morphological and Growth Characteristics of MCF-7 Cells.- 7.3.2 Growth of MCF-7 Cells in Tridimensional Matrix.- 7.3.3 Growth of MCF-7 Cells in Athymic Mice.- 7.4 Growth Properties of Immortal Human Breast Epithelial Cells In Vitro.- 7.4.1 Telomerase Activation.- 7.4.2 Abrogation of Cell Cycle Control.- 7.4.3 Genes Preferentially Expressed During Cell Immortalization.- 7.5 Transformation of Primary Cultures of Human Breast Epithelial Cells with Chemical Carcinogens.- 7.6 In Vitro System of Cell Transformation.- 7.6.1 Transformation of Human Breast Epithelial Cells with c-Ha-ras Oncogene.- 7.6.2 Transformation of Human Breast Epithelial Cells with Chemical Carcinogens.- 7.6.3 Ha-ras Enhances the Transformation of Human Breast Epithelial Cells with Chemical Carcinogens.- References.- 8 Genomic Basis of Breast Cancer.- 8.1 Introduction.- 8.2 Genomic Changes Observed in Breast Cancer.- 8.3 Microsatellite Instability as an Early Genomic Event in Breast Cancer Initiation.- 8.4 Other Genomic Changes Associated with Immortalization, Transformation, and Tumorigenesis.- 8.4.1 Tumor Suppressor Gene p53.- 8.4.2 Oncogenes.- 8.4.2.1 c-Ha-ras.- 8.4.2.2 c-neu, int-2, and c-myc Oncogenes.- 8.4.3 mdm2 Gene.- 8.4.4 Loss of Heterozygosity and Fluorescence In Situ Hybridization Analysis of Chromosome 17p.- 8.5 Search for Specific Functional Relevance of the Genomic Changes.- 8.5.1 Reversion of the Immortalization Phenotype.- 8.5.2 Reversion of the Transformation but Not Immortalization Phenotype.- 8.6 The Role of Mismatch Repair in the Initial Event of Carcinogenesis.- 8.7 Unifying Concepts.- References.- 9 Preventive Strategies in Breast Cancer.- 9.1 Introduction.- 9.2 Physicoprevention with Prophylactic Mastectomy.- 9.3 Bioprevention of Hereditary Breast Cancer.- 9.4 Chemoprevention Against Acquired Somatic Mutations.- 9.4.1 Limiting Accumulation of Chemical Carcinogens.- 9.4.2 Enhancing Excretion of Xenobiotics.- 9.4.2.1 Organosulfur Compounds.- 9.4.2.2 Indole-3-Carbinol.- 9.4.2.3 Phytoalexin.- 9.4.2.4 Triterpenoids.- 9.4.3 Eliminating Oxidative Stress.- 9.4.3.1 Carotenoids.- 9.4.3.2 Vitamin E and Selenium.- 9.4.3.3 Tea and Polyphenolic Antioxidants.- 9.4.3.4 Flavonoids.- 9.5 Chemoprevention Against Epigenetic Alterations.- 9.5.1Restricting Fat Caloric Consumption.- 9.5.2Maintaining Proper Endocrine Milieu.- 9.5.2.1 Steroids.- 9.5.2.2 Aromatase Inhibitors.- 9.5.2.3 Estrone Sulfatase Inhibitors.- 9.5.2.4 Dehydroepiandrosterone.- 9.5.2.5 Genistein.- 9.6 Melatonin.- 9.7 Eicosanoids.- 9.8 Estrogen Antagonists.- 9.8.1 Antiestrogens.- 9.8.2 Aryl Hydrocarbon Receptor Agonists.- 9.9 Interrupting Carcinogenic Signal Transduction.- 9.9.1 Inhibitors of Receptor Tyrosine Kinases.- 9.9.2 Inhibitors of p21ras Farnesylation.- 9.9.3 Inhibitors of HMG-CoA Reductase.- 9.9.4 Monoterpenes.- 9.9.5 Eicosapentaenoic Acid.- 9.10 Inducing Breast Cell Differentiation.- 9.10.1 Retinoids.- 9.10.2 Pregnancy and Human Chorionic Gonadotropin.- 9.11 N-Chemoprevention Against Growth of Neoplasms: Suppressing the Growth of Neoplastic Cells.- 9.11.1 Vitamin D and Calcium.- 9.11.2 Ornithine Decarboxylase Inhibitors.- 9.12 O-Inhibiting Neovascularization or Angiogenesis.- 9.13 Socioprevention of Breast Cancer.- 9.14 Summary and Future Perspectives.- References.- 10 The New Paradigm in Breast Cancer Prevention.- 10.1 Rationale for a New Paradigm.- 10.2 The New Paradigm.- 10.3 Epidemiological and Clinical Basis for the New Paradigm.- 10.4 Data from Experimental Animal Studies.- 10.4.1 Pregnancy.- 10.4.2 Placental Hormones.- 10.4.3 Estrogenic and Progestagenic Agents.- 10.4.4 Role of Pregnancy and Chorionic Gonadotropin in Mammary Gland Differentiation and Cancer Initiation.- 10.5 Role of Human Chorionic Gonadotropin in Breast Cancer Progression.- 10.5.1 Mammary Gland Development Under Influence of Human Chorionic Gonadotropin.- 10.5.2 Hormonal Profile Induced by Human Chorionic Gonadotropin.- 10.5.3 Effect of Human Chorionic Gonadotropin on Terminal End Buds, Intraductal Proliferations, and Ductal Carcinomas In Situ.- 10.5.4 Effect of Human Chorionic Gonadotropin Treatment on DMBA-Induced Tumor Progression.- 10.6 Effect of Human Chorionic Gonadotropin on Inhibin Expression and Its Relation with the Activation of Early Response Genes.- 10.7 Effect of Human Chorionic Gonadotropin on Programmed Cell Death Gene Expression.- 10.7.1 Effect of Human Chorionic Gonadotropin in the Mammary Gland of Animals Treated with DMBA.- 10.7.2 Effect of Human Chorionic Gonadotropin Treatment on the Expression of Apoptotic Genes in DMBA-Induced Mammary Carcinomas.- 10.7.3 Effect of Human Chorionic Gonadotropin Treatment on the Expression of Apoptotic Genes in the Ovary.- 10.7.4 Effect of Human Chorionic Gonadotropin Treatment on Apoptosis.- 10.8 Evidence of a Direct Effect of Human Chorionic Gonadotropin in Mammary Epithelial Cells.- 10.8.1 Human Chorionic Gonadotropin Has an Inhibitory Effect on DMBA Mammary Carcinogenesis in Ovariectomized Animals.- 10.8.2 Effect of Human Chorionic Gonadotropin in Human Breast Epithelial Cells In Vitro.- 10.9 Tumoristatic Effect of Human Chorionic Gonadotropin on Malignant Human Breast Epithelial Cells Transplanted in Heterologous Host.- 10.10 Effect of Recombinant Human Chorionic Gonadotropin on Primary Breast Cancer.- 10.11 Isolation and Characterization of New Genes Induced by Human Chorionic Gonadotropin.- 10.11.1 Genes Induced by Human Chorionic Gonadotropin in Human Breast Epithelial Cells In Vitro.- 10.11.2 Genes Induced by Human Chorionic Gonadotropin in the Rat Mammary Gland.- 10.11.2.1Morphological Phenotypes Induced by Urinary and Recombinant Human Chorionic Gonadotropin.- 10.11.2.2 Differential Display and Northern Blot Analysis.- 10.12 Genomic Signature Induced by Human Chorionic Gonadotropin and Pregnancy.- 10.13 Unifying Concepts.- References.

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